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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Oncol.</journal-id>
<journal-title>Frontiers in Oncology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Oncol.</abbrev-journal-title>
<issn pub-type="epub">2234-943X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fonc.2024.1403666</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Oncology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Clinical significance of the modified Naples prognostic score in patients with stage II-III colon cancer undergoing curative resection: a retrospective study from the real world</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Xiaopeng</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2570306"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Cheng</surname>
<given-names>Chen</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huo</surname>
<given-names>Xiongwei</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhao</surname>
<given-names>Chenye</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Yuan</surname>
<given-names>Hang</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Gang</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Yu</surname>
<given-names>Junhui</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1329671"/>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Mu</surname>
<given-names>Mingchao</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1921617"/>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Sun</surname>
<given-names>Xuejun</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1243672"/>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Department of General Surgery, the First Affiliated Hospital of Xi&#x2019;an Jiaotong University</institution>, <addr-line>Xi&#x2019;an</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Gynecologic Oncology, the Shaanxi Provincial Cancer Hospital</institution>, <addr-line>Xi&#x2019;an</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Sharon R. Pine, University of Colorado Anschutz Medical Campus, United States</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Vincenzo Quagliariello, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Italy</p>
<p>Johannes Doerner, Helios Klinikum Wuppertal, Germany</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Mingchao Mu, <email xlink:href="mailto:mumingchao@mail.xjtu.edu.cn">mumingchao@mail.xjtu.edu.cn</email>; Xuejun Sun, <email xlink:href="mailto:sunxy@mail.xjtu.edu.cn">sunxy@mail.xjtu.edu.cn</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>16</day>
<month>09</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>14</volume>
<elocation-id>1403666</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>04</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>27</day>
<month>08</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Li, Cheng, Huo, Zhao, Yuan, Chen, Yu, Mu and Sun</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Li, Cheng, Huo, Zhao, Yuan, Chen, Yu, Mu and Sun</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>The Naples prognostic score (NPS) determined by the nutritional and inflammatory condition of an individual is attracting growing attention for predicting postoperative outcomes in a variety of malignancies. The study aimed to assess the clinical significance of a modified NPS (M-NPS) and establish and validate nomograms incorporating M-NPS in curative stage II-III colon cancer patients.</p>
</sec>
<sec>
<title>Methods</title>
<p>We retrospectively analyzed 328 stage II-III colon cancer patients receiving radical surgical resection at our hospital from January 2011 to December 2016. Kaplan&#x2013;Meier (KM) survival analysis and Cox regression analysis were executed for overall survival (OS) and cancer-specific survival (CSS). Independent predictive indicators were applied to develop nomograms. The model&#x2019;s performance was evaluated using many different methods.</p>
</sec>
<sec>
<title>Results</title>
<p>Of a total of 328 cases, 153 cases were in group 0, 145 in group 1, and 30 in group 2. In terms of OS or CSS, there were obvious differences between groups 0 and 1, and between groups 0 and 2. Age, obstruction, N stage, gross tumor type, and M-NPS group were independent prognostic indicators for OS, while obstruction, gross tumor type, M-NPS group, and N stage were independent predictive parameters for CSS. Furthermore, the training and validation sets were randomly allocated among a cohort of 328 patients. OS and CSS prediction nomograms were developed. In the training and validation cohort, the C-index and ROC analysis showed good discrimination, calibration curves exhibited an excellent level of consistency between model-predicted survival and actual survival outcomes, and DCA curves demonstrated good clinical performance.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>M-NPS is a reliable survival predictor in patients with curative stage II-III colon cancer. Nomograms incorporating M-NPS for OS and CSS have good predictive performance and clinical utility.</p>
</sec>
</abstract>
<kwd-group>
<kwd>colon cancer</kwd>
<kwd>modified Naples prognostic score</kwd>
<kwd>prognostic factors</kwd>
<kwd>curative resection</kwd>
<kwd>nomogram</kwd>
</kwd-group>
<counts>
<fig-count count="6"/>
<table-count count="5"/>
<equation-count count="0"/>
<ref-count count="52"/>
<page-count count="16"/>
<word-count count="5480"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Gastrointestinal Cancers: Colorectal Cancer</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<title>Introduction</title>
<p>Colorectal cancer (CRC) ranks third in prevalence and is the second leading cause of cancer deaths globally, according to recent statistics (<xref ref-type="bibr" rid="B1">1</xref>). Smoking, alcohol, obesity, diabetes, poor diets and low physical activity increase CRC risk (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B3">3</xref>). Approximately 50% of colon cancer patients are stage II or III at the time of diagnosis (<xref ref-type="bibr" rid="B4">4</xref>). Radical surgery is the primary therapeutic approach for II-III colon cancer (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>). Although surgical resection significantly improves the survival of stage II-III patients, postoperative prognostic monitoring of these individuals continues to be a great challenge as a result of the disease&#x2019;s highly heterogeneous nature. The current widely accepted prognostic assessment of colon cancer is based on postoperative pathological indicators (<xref ref-type="bibr" rid="B6">6</xref>). These histological factors can be obtained for assessment only after surgery. Therefore, the identification of a preoperatively available prognostic marker is extremely important for physicians&#x2019; clinical decision-making and prognostic risk stratification.</p>
<p>It is generally accepted that the prognosis of cancer individuals is influenced not only by the biology of the cancer but also by host-related conditions (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>). Inflammation, a leading hallmark of cancer, has a significant impact on tumorigenesis and progression (<xref ref-type="bibr" rid="B9">9</xref>). The cytokine release mediated by the NLRP3 inflammasome in various cell types contributes to the formation of an inflammatory tumor microenvironment through autocrine and paracrine signaling mechanisms (<xref ref-type="bibr" rid="B10">10</xref>). In colon cancer, activation of NLRP3 functions as a tumor suppressor by mediating the production of IL-18, which reinforces the killing activity of natural killer cells against metastatic tumor cells or down-regulates IL-22BP to suppress tumorigenesis (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B11">11</xref>). The nutritional, inflammatory, and immune conditions of individuals are thought to be tightly associated with the outcome of CRC (<xref ref-type="bibr" rid="B12">12</xref>&#x2013;<xref ref-type="bibr" rid="B18">18</xref>). Prior research has indicated that a variety of serum inflammation-related biomarkers can be beneficial for assessing the outcome in CRC (<xref ref-type="bibr" rid="B17">17</xref>), such as neutrophil-to-lymphocyte ratio (NLR) (<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B20">20</xref>), platelet-to-lymphocyte ratio (PLR) (<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>) and lymphocyte-to-monocyte ratio (LMR) (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>). Additionally, several scoring systems, including the controlling nutritional status score (<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B26">26</xref>), the systemic inflammation score (<xref ref-type="bibr" rid="B27">27</xref>), the prognostic nutritional index (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B28">28</xref>), and the Glasgow prognostic score (<xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B29">29</xref>), had been confirmed as promising predictive markers for CRC outcome. NPS, a new scoring system to assess cancer outcomes, has attracted widespread attention. NPS based on inflammatory and nutritional status, first defined by Gennaro et&#xa0;al., is constructed from total cholesterol (CHOL), serum albumin (ALB), LMR, and NLR (<xref ref-type="bibr" rid="B30">30</xref>). Currently, the prognostic significance of NPS in CRC, obstructive CRC, metastatic CRC (mCRC) and rectal cancer has been reported by related studies (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B30">30</xref>&#x2013;<xref ref-type="bibr" rid="B32">32</xref>). The clinical significance of NPS in stage II-III patients, particularly in those receiving radical resection, has yet to be documented.</p>
<p>This study aims to construct a M-NPS for stage II-III patients, assess its prognostic value, and create a nomogram to forecast survival outcomes.</p>
</sec>
<sec id="s2">
<title>Patients and methods</title>
<sec id="s2_1">
<title>Patient cohort</title>
<p>This study ultimately enrolled 328 stage II-III colon cancer patients, who underwent curative surgical resection at the Department of General Surgery, the First Affiliated Hospital of Xi&#x2019;an Jiaotong University from January 2011 to December 2016 (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>). All subjects were diagnosed with preoperative biopsy or postoperative pathological examination. All patients were diagnosed with colon cancer and not in combination with other cancers, and none of them underwent neoadjuvant chemotherapy before surgery. The following were the exclusion criteria: definite inflammatory or hematologic diseases affecting immune or nutritional status; unknown prognostic information due to lost to follow-up; missing blood test results within one week before surgery. Patients were followed up via outpatient services or telephone interviews to obtain their health condition. The follow-up concluded in December 2022. The outcome was specified as either OS or CSS. OS was described as the interval between the surgical procedure and mortality resulting from any cause. The period from surgery to mortality as a result of recurrence or metastasis of the primary malignancy was referred to as CSS. For CSS, a patient&#x2019;s death was defined as a non-endpoint event if the cause of death was not due to cancer. Cases lacking an outcome event were censored in the analysis.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Flowchart for identifying the study population. CSS, cancer-specific survival.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g001.tif"/>
</fig>
</sec>
<sec id="s2_2">
<title>Data gathering</title>
<p>The clinicopathological indicators extracted from the patient&#x2019;s electronic health data include age, sex, underlying disease, anemia, tumor location, American Society of Anesthesiologists (ASA) classification, surgical approach, ascites, intestinal perforation, obstruction, tumor size, gross tumor type, pathology type, differentiation, N stage, T stage, TNM stage, lymph node dissection, perineural invasion, vessel invasion and chemotherapy. Laboratory examinations within one week before surgery include ALB, CHOL, total counts of neutrophils, lymphocytes, and monocytes.</p>
</sec>
<sec id="s2_3">
<title>Construction of M-NPS</title>
<p>M-NPS is a scoring system calculated from four factors: ALB, CHOL, LMR and NLR. Given that traditional NPS failed to exhibit substantial clinical utility in the study population, X-Tile 3.6.1 software (Yale University, New Haven, USA) (<xref ref-type="bibr" rid="B33">33</xref>) was employed to identify the most suitable threshold value for the four indicators according to the maximum chi-square and the lowest <italic>P</italic> values of log-rank tests (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2</bold>
</xref>). <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref> provides the comprehensive scoring criteria for the M-NPS. Patients were classified into three groups according to their total M-NPS scores: group 1 for scores of 0, group 2 for scores of 1-2, and group 3 for scores of 3-4.</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Optimal cutoff values were identified by the X-Tile analysis. The plots showed the &#x3c7; 2 log&#x2010;rank values produced when dividing the cohort into two groups with optimal cut-points. Red coloration of cut points indicates an inverse correlation with survival, while green ones positively correlate. The optimal cutoff values highlighted by the black circles in the left panels are displayed in histograms of the entire cohort (middle panels), and Kaplan&#x2013;Meier plots are shown in the right panels. For overall survival, the optimal thresholds for ALB <bold>(A)</bold>, CHOL <bold>(B)</bold>, NLR <bold>(C)</bold>, and LMR <bold>(D)</bold> were identified as 30.9 g/L, 3.6 mmol/L, 4.06, and 1.72, respectively.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g002.tif"/>
</fig>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Scoring criteria of the modified Naples prognostic score (M-NPS).</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Variables</th>
<th valign="top" align="center">Cutoff value</th>
<th valign="top" align="center">Points</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="2" align="left">Serum albumin (g/L)</td>
<td valign="top" align="center">&gt;30.9</td>
<td valign="top" align="center">0</td>
</tr>
<tr>
<td valign="top" align="center">&#x2264;30.9</td>
<td valign="top" align="center">1</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">Total cholesterol (mmol/L)</td>
<td valign="top" align="center">&gt;3.6</td>
<td valign="top" align="center">0</td>
</tr>
<tr>
<td valign="top" align="center">&#x2264;3.6</td>
<td valign="top" align="center">1</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">NLR</td>
<td valign="top" align="center">&gt;4.06</td>
<td valign="top" align="center">1</td>
</tr>
<tr>
<td valign="top" align="center">&#x2264;4.06</td>
<td valign="top" align="center">0</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">LMR</td>
<td valign="top" align="center">&gt;1.72</td>
<td valign="top" align="center">0</td>
</tr>
<tr>
<td valign="top" align="center">&#x2264;1.72</td>
<td valign="top" align="center">1</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s2_4">
<title>Procedures of treatment</title>
<p>All curative surgeries for patients enrolled in the study were conducted by a skilled surgical team. They underwent open resection or laparoscopic operation, subject to the location of the disease and the surgical team&#x2019;s preference. Adjuvant chemotherapy was implemented within two months postoperatively according to pathologic TNM staging results and the patient&#x2019;s condition. Some patients discontinue chemotherapy midway because they cannot tolerate the side effects.</p>
</sec>
<sec id="s2_5">
<title>Statistical analysis</title>
<p>The medians and interquartile ranges (IQRs) of continuous variables are shown, while categorical variables are described as percentages and numbers. Continuous variables were compared by the <italic>Kruskal</italic>-Waills test or the <italic>Mann-Whitney U</italic> test. For comparison of categorical variables between two or more groups, <italic>chi-square</italic> or <italic>Fisher&#x2019;s</italic> exact tests were implemented. The survival and survminer R packages were employed to plot KM survival curves and compared their survival rates with a <italic>log-rank</italic> test. Independent prognostic analysis for OS or CSS was determined by multivariate Cox regression. A multivariate analysis was performed only on parameters with P&lt;0.05 in a univariate analysis. The dataset was randomly divided in 6.5:3.5 into training and validation sets using the sample function. Independent prognostic variables were employed to develop nomograms in the training set using the rms R package. The model discrimination can be assessed with the C-index and the ROC curve. The calibration curve was generated with the rms R package to evaluate the prediction ability of the model. Additionally, the DCA was employed to evaluate the clinical efficacy of the model using the ggDCA R package. Version 4.3.2 of the R software was used to conduct all statistical analyses. Statistical tests with P&lt; 0.05 are significantly difference.</p>
</sec>
</sec>
<sec id="s3" sec-type="results">
<title>Results</title>
<sec id="s3_1">
<title>Patients&#x2019; baseline features and connection between M-NPS and clinicopathological parameters of patients</title>
<p>
<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref> displays the inclusion of 328 patients in the ultimate statistical analysis. Of the 328 patients, the age at diagnosis had a median value of 62 years. The research comprised 165 male and 163 female participants. The study subjects consisted of 113 patients with underlying diseases and 215 patients without underlying diseases. There were 148 patients with left hemicolon cancers, while 180 patients had right hemicolon cancers. 199 patients received open resection and 129 underwent laparoscopic surgery (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>). The median OS and CSS were both 86 months. Based on M-NPS scores, the cohort was stratified into three groups: 153 patients in group 0, 145 in group 1, and 30 in group 2. Of all clinicopathologic features, male, no underlying disease, open surgery and larger tumor size were associated with higher M-NPS scores. Lower ASA classification, ascites, no intestinal perforation, no obstruction and chemotherapy were related to lower M-NPS scores (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>). In addition, ALB, CHOL and LMR were all negatively correlated with M-NPS scores, whereas NLR was positively related to M-NPS scores (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>).</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Association of modified Naples prognostic score and clinicopathological characteristics in 328 stage II-III colon cancer patients.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Variables</th>
<th valign="top" align="center">Group 0<break/>(<italic>n</italic> = 153)</th>
<th valign="top" align="center">Group 1<break/>(<italic>n</italic> = 145)</th>
<th valign="top" align="center">Group 2<break/>(<italic>n</italic> = 30)</th>
<th valign="top" align="center">
<italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age, M (Q<sub>1</sub>, Q<sub>3</sub>)</td>
<td valign="top" align="center">62 (52,71)</td>
<td valign="top" align="center">63 (49,71)</td>
<td valign="top" align="center">65 (56,75)</td>
<td valign="top" align="center">0.302</td>
</tr>
<tr>
<td valign="top" align="left">Sex, <italic>n</italic> (%)<break/>&#x2003;Female<break/>&#x2003;Male</td>
<td valign="top" align="center">
<break/>98 (64.1)<break/>55 (35.9)</td>
<td valign="top" align="center">
<break/>53 (35.9)<break/>93 (64.1)</td>
<td valign="top" align="center">
<break/>13 (43.3)<break/>17 (56.7)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Underlying disease, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>91 (59.5)<break/>62 (40.5)</td>
<td valign="top" align="center">
<break/>106 (73.1)<break/>39 (26.9)</td>
<td valign="top" align="center">
<break/>18 (60.0)<break/>12 (40.0)</td>
<td valign="top" align="center">0.037</td>
</tr>
<tr>
<td valign="top" align="left">Anemia, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>69 (45.1)<break/>84 (54.9)</td>
<td valign="top" align="center">
<break/>54 (37.2)<break/>91 (62.8)</td>
<td valign="top" align="center">
<break/>11 (36.7)<break/>19 (63.3)</td>
<td valign="top" align="center">0.343</td>
</tr>
<tr>
<td valign="top" align="left">Tumor location, <italic>n</italic> (%)<break/>&#x2003;Left hemicolon<break/>&#x2003;Right hemicolon</td>
<td valign="top" align="center">
<break/>79 (51.6)<break/>74 (48.4)</td>
<td valign="top" align="center">
<break/>55 (37.9)<break/>90 (62.1)</td>
<td valign="top" align="center">
<break/>14 (46.7)<break/>16 (53.3)</td>
<td valign="top" align="center">0.059</td>
</tr>
<tr>
<td valign="top" align="left">ASA, <italic>n</italic> (%)<break/>&#x2003;1/2<break/>&#x2003;3/4</td>
<td valign="top" align="center">
<break/>119 (77.8)<break/>34 (22.2)</td>
<td valign="top" align="center">
<break/>100 (69.6)<break/>45 (30.4)</td>
<td valign="top" align="center">
<break/>15 (50.0)<break/>15 (50.0)</td>
<td valign="top" align="center">0.006</td>
</tr>
<tr>
<td valign="top" align="left">Surgical approach, <italic>n</italic> (%)<break/>&#x2003;Laparoscopic<break/>&#x2003;Open</td>
<td valign="top" align="center">
<break/>71 (46.4)<break/>82 (53.6)</td>
<td valign="top" align="center">
<break/>50 (34.5)<break/>95 (65.5)</td>
<td valign="top" align="center">
<break/>8 (26.7)<break/>22 (73.3)</td>
<td valign="top" align="center">0.036</td>
</tr>
<tr>
<td valign="top" align="left">Ascites, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>138 (90.2)<break/>15 (9.8)</td>
<td valign="top" align="center">
<break/>120 (82.8)<break/>25 (17.2)</td>
<td valign="top" align="center">
<break/>18 (60.0)<break/>12 (40.0)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Intestinal perforation, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>153 (100.0)<break/>0 (0.0)</td>
<td valign="top" align="center">
<break/>141 (97.2)<break/>4 (2.8)</td>
<td valign="top" align="center">
<break/>27 (90.0)<break/>3 (10.0)</td>
<td valign="top" align="center">0.003</td>
</tr>
<tr>
<td valign="top" align="left">Obstruction, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>115 (75.2)<break/>&#x2003;38 (24.8)</td>
<td valign="top" align="center">
<break/>94 (64.8)<break/>51 (35.2)</td>
<td valign="top" align="center">
<break/>12 (40.0)<break/>18 (60.0)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Tumor size, n (%)<break/>&#x2003;&#x2264; 5 cm<break/>&#x2003;&gt; 5 cm</td>
<td valign="top" align="center">
<break/>108 (70.6)<break/>45 (29.4)</td>
<td valign="top" align="center">
<break/>82 (56.5)<break/>63 (43.5)</td>
<td valign="top" align="center">
<break/>10 (33.3)<break/>20 (66.7)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Gross tumor type, <italic>n</italic> (%)<break/>&#x2003;Infiltrative<break/>&#x2003;Ulcerated<break/>&#x2003;Elevated</td>
<td valign="top" align="center">
<break/>5 (3.3)<break/>107 (69.9)<break/>41 (26.8)</td>
<td valign="top" align="center">
<break/>7 (4.8)<break/>99 (68.3)<break/>39 (26.9)</td>
<td valign="top" align="center">
<break/>2 (6.7)<break/>14 (46.6)<break/>14 (46.7)</td>
<td valign="top" align="center">0.153</td>
</tr>
<tr>
<td valign="top" align="left">Pathology type, <italic>n</italic> (%)<break/>&#x2003;Adenocarcinoma<break/>&#x2003;Mucinous adenocarcinoma<break/>&#x2003;Mixed</td>
<td valign="top" align="center">
<break/>132 (86.3)<break/>9 (5.9)<break/>12 (7.8)</td>
<td valign="top" align="center">
<break/>115 (79.3)<break/>18 (12.4)<break/>12 (8.3)</td>
<td valign="top" align="center">
<break/>24 (80.0)<break/>3 (10.0)<break/>3 (10.0)</td>
<td valign="top" align="center">0.291</td>
</tr>
<tr>
<td valign="top" align="left">Differentiation, <italic>n</italic> (%)<break/>&#x2003;Well<break/>&#x2003;Moderately<break/>&#x2003;Poorly</td>
<td valign="top" align="center">
<break/>3 (2.0)<break/>135 (88.2)<break/>15 (9.8)</td>
<td valign="top" align="center">
<break/>5 (3.5)<break/>125 (86.2)<break/>15 (10.3)</td>
<td valign="top" align="center">
<break/>0 (0.0)<break/>23 (76.7)<break/>7 (23.3)</td>
<td valign="top" align="center">0.248</td>
</tr>
<tr>
<td valign="top" align="left">T stage, <italic>n</italic> (%)<break/>&#x2003;T2/ T3<break/>&#x2003;T4</td>
<td valign="top" align="center">
<break/>23 (15.0)<break/>130 (85.0)</td>
<td valign="top" align="center">
<break/>20 (13.8)<break/>125 (86.2)</td>
<td valign="top" align="center">
<break/>4 (13.3)<break/>26 (86.7)</td>
<td valign="top" align="center">0.942</td>
</tr>
<tr>
<td valign="top" align="left">N stage, <italic>n</italic> (%)<break/>&#x2003;N0<break/>&#x2003;N1<break/>&#x2003;N2</td>
<td valign="top" align="center">
<break/>100 (65.4)<break/>44 (28.8)<break/>9 (5.8)</td>
<td valign="top" align="center">
<break/>86 (59.3)<break/>41 (28.3)<break/>18 (12.4)</td>
<td valign="top" align="center">
<break/>21 (70.0)<break/>6 (20.0)<break/>3 (10.0)</td>
<td valign="top" align="center">0.298</td>
</tr>
<tr>
<td valign="top" align="left">Lymph node dissection, <italic>n</italic> (%)<break/>&#x2003;&lt; 12<break/>&#x2003;&#x2265; 12</td>
<td valign="top" align="center">
<break/>40 (26.1)<break/>113 (73.9)</td>
<td valign="top" align="center">
<break/>26 (17.9)<break/>119(82.1)</td>
<td valign="top" align="center">
<break/>10 (33.3)<break/>20 (66.7)</td>
<td valign="top" align="center">0.094</td>
</tr>
<tr>
<td valign="top" align="left">Perineural invasion, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>146 (95.4)<break/>7 (4.6)</td>
<td valign="top" align="center">
<break/>136 (93.8)<break/>9 (6.2)</td>
<td valign="top" align="center">
<break/>28 (93.3)<break/>2 (6.7)</td>
<td valign="top" align="center">0.790</td>
</tr>
<tr>
<td valign="top" align="left">Vessel invasion, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>144 (94.1)<break/>9 (5.9)</td>
<td valign="top" align="center">
<break/>138 (95.2)<break/>7 (4.8)</td>
<td valign="top" align="center">
<break/>29 (96.7)<break/>1 (3.3)</td>
<td valign="top" align="center">0.819</td>
</tr>
<tr>
<td valign="top" align="left">Chemotherapy, <italic>n</italic> (%)<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="center">
<break/>47 (30.8)<break/>106 (69.3)</td>
<td valign="top" align="center">
<break/>57 (39.3)<break/>88 (60.7)</td>
<td valign="top" align="center">
<break/>18 (60.0)<break/>12 (40.0)</td>
<td valign="top" align="center">0.008</td>
</tr>
<tr>
<td valign="top" align="left">ALB (g/L), M (Q<sub>1</sub>, Q<sub>3</sub>)</td>
<td valign="top" align="center">37.6 (35.5, 40.5)</td>
<td valign="top" align="center">36.3 (32.9, 38.9)</td>
<td valign="top" align="center">30.2 (28.7, 33.5)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">CHOL (mmol/L), M (Q<sub>1</sub>, Q<sub>3</sub>)</td>
<td valign="top" align="center">4.3 (3.9, 4.7)</td>
<td valign="top" align="center">3.4 (3.1, 3.8)</td>
<td valign="top" align="center">3.1 (2.9, 3.3)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">NLR, M (Q<sub>1</sub>, Q<sub>3</sub>)</td>
<td valign="top" align="center">2.0 (1.5, 2.6)</td>
<td valign="top" align="center">2.8 (2.0, 4.4)</td>
<td valign="top" align="center">6.1 (5.0, 7.6)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
<tr>
<td valign="top" align="left">LMR, M (Q<sub>1</sub>, Q<sub>3</sub>)</td>
<td valign="top" align="center">4.4 (3.2, 5.8)</td>
<td valign="top" align="center">3.0 (2.1, 4.5)</td>
<td valign="top" align="center">1.6 (1.2, 1.8)</td>
<td valign="top" align="center">&lt;0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>M, Median; Q<sub>1</sub>, 1st Quartile; Q<sub>3</sub>, 3st Quartile.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3_2">
<title>Patient&#x2019;s prognosis (OS and CSS) according to M-NPS</title>
<p>Survival analysis of OS and CSS based on M-NPS grouping was performed and survival curves were plotted in <xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>. For OS in stage II-III patients, the median survival for group 2 was 95 months. Group 0 had more favorable survival than both group 1 and group 2 (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3A</bold>
</xref>). Further stratified survival analysis using staging showed that in comparison to group 0 and group 1, group 2 had the poorest prognosis for stage II patients (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3B</bold>
</xref>). In stage III patients, group 0 had superior survival than group 1 (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3C</bold>
</xref>), and a significant survival difference was not observed between group 1 and 2, nor between group 0 and 2. In terms of CSS for stage II-III patients, the median survival time in group 2 was 119 months. Group 0 had the best survival compared to group 1 and group 2 (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3D</bold>
</xref>). Similarly, among stage II patients, group 2 had poorer CSS compared to those in group 1 and 0 (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3E</bold>
</xref>). For stage III patients, group 0 had the most favorable CSS, and the remaining two groups did not appear to differ markedly in survival (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3F</bold>
</xref>).</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>Kaplan&#x2013;Meier survival curves of OS and CSS for each M-NPS group. Differences in OS among the three groups in patients with stage II-III <bold>(A)</bold>, II <bold>(B)</bold>, and III <bold>(C)</bold> colon cancer. Differences in CSS among the three groups in patients with stage II-III <bold>(D)</bold>, II <bold>(E)</bold>, and III <bold>(F)</bold> colon cancer. OS, overall survival; CSS, cancer-specific survival.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g003.tif"/>
</fig>
</sec>
<sec id="s3_3">
<title>Univariate and multivariate analyses of prognostic factors for OS and CSS</title>
<p>We conducted univariate and multivariate Cox regression analysis on OS for stage II-III patients. The results are displayed in <xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>. OS had a strong association with the M-NPS group, as indicated by the univariate analysis. Additional multivariate analysis revealed that the M-NPS group was an independent risk indicator for OS. Group 1 and group 2 had worse OS compared to group 0 [G1 vs G0: 1.73 (1.05&#x2013;2.86); G2 vs G0: 2.55 (1.29&#x2013;5.03)]. Other independent prognostic risk indicators included age, obstruction, gross tumor type, and N stage.</p>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Univariate and multivariate analyses of the prognostic factor for OS.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" rowspan="2" align="left">Variables</th>
<th valign="top" colspan="2" align="center">Univariate analysis</th>
<th valign="top" colspan="2" align="center">Multivariate analysis</th>
</tr>
<tr>
<th valign="top" align="center">HR (95% CI)</th>
<th valign="top" align="center">
<italic>P</italic>-value</th>
<th valign="top" align="center">HR (95% CI)</th>
<th valign="top" align="center">
<italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age</td>
<td valign="top" align="left">1.03 (1.02-1.05)</td>
<td valign="top" align="center">&lt;0.001</td>
<td valign="middle" align="left">1.03 (1.01-1.05)</td>
<td valign="top" align="center">0.013<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Sex<break/>&#x2003;Female<break/>&#x2003;Male</td>
<td valign="top" align="left">
<break/>Reference<break/>1.30 (0.86-1.97)</td>
<td valign="top" align="center">
<break/>
<break/>0.205</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Underlying disease<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>1.16 (0.76-1.76)</td>
<td valign="top" align="center">
<break/>
<break/>0.495</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Anemia<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>1.01 (0.67-1.53)</td>
<td valign="top" align="center">
<break/>
<break/>0.946</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Tumor location<break/>&#x2003;Right hemicolon<break/>&#x2003;Left hemicolon</td>
<td valign="top" align="left">
<break/>Reference<break/>0.95 (0.63-1.42)</td>
<td valign="top" align="center">
<break/>
<break/>0.788</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">ASA<break/>&#x2003;1/2<break/>&#x2003;3/4</td>
<td valign="middle" align="left">
<break/>Reference<break/>2.23 (1.48-3.36)</td>
<td valign="middle" align="center">
<break/>
<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>1.21 (0.73-2.01)</td>
<td valign="top" align="center">
<break/>
<break/>0.453</td>
</tr>
<tr>
<td valign="top" align="left">Surgical approach<break/>&#x2003;Laparoscopic<break/>&#x2003;Open</td>
<td valign="top" align="left">
<break/>Reference<break/>1.58 (1.02-2.47)</td>
<td valign="top" align="center">
<break/>
<break/>0.042</td>
<td valign="top" align="left">
<break/>Reference<break/>1.33 (0.83-2.13)</td>
<td valign="top" align="center">
<break/>
<break/>0.230</td>
</tr>
<tr>
<td valign="top" align="left">Ascites<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="middle" align="left">
<break/>Reference<break/>2.03 (1.27-3.26)</td>
<td valign="middle" align="center">
<break/>
<break/>0.003</td>
<td valign="top" align="left">
<break/>Reference<break/>0.86 (0.49-1.50)</td>
<td valign="top" align="center">
<break/>
<break/>0.585</td>
</tr>
<tr>
<td valign="top" align="left">Intestinal perforation<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>1.98 (0.63-6.25)</td>
<td valign="top" align="center">
<break/>
<break/>0.246</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Obstruction<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.51 (1.67-3.77)</td>
<td valign="top" align="center">
<break/>
<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>2.21 (1.38-3.52)</td>
<td valign="top" align="center">
<break/>
<break/>0.001<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Tumor size<break/>&#x2003;&#x2264; 5 cm<break/>&#x2003;&gt; 5 cm</td>
<td valign="top" align="left">
<break/>Reference<break/>1.00 (0.66-1.52)</td>
<td valign="top" align="center">
<break/>
<break/>0.997</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Gross tumor type<break/>&#x2003;Infiltrative<break/>&#x2003;Ulcerated<break/>&#x2003;Elevated</td>
<td valign="middle" align="left">
<break/>Reference<break/>0.67 (0.29-1.54)<break/>0.29 (0.11-0.75)</td>
<td valign="middle" align="center">
<break/>
<break/>0.347<break/>0.011</td>
<td valign="top" align="left">
<break/>Reference<break/>0.49 (0.20-1.20)<break/>0.23 (0.08-0.61)</td>
<td valign="top" align="center">
<break/>
<break/>0.120<break/>0.003<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Pathology type<break/>&#x2003;Adenocarcinoma<break/>&#x2003;Mucinous<break/>&#x2003;Mixed</td>
<td valign="top" align="left">
<break/>Reference<break/>0.88 (0.43-1.83)<break/>0.83 (0.38-1.80)</td>
<td valign="top" align="center">
<break/>
<break/>0.738<break/>0.641</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Differentiation<break/>&#x2003;Well<break/>&#x2003;Moderately<break/>&#x2003;Poorly</td>
<td valign="top" align="left">
<break/>Reference<break/>0.71 (0.22-2.24)<break/>0.71 (0.19-2.57)</td>
<td valign="top" align="center">
<break/>
<break/>0.556<break/>0.599</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">T stage<break/>&#x2003;T2 &amp; T3<break/>&#x2003;T4</td>
<td valign="top" align="left">
<break/>Reference<break/>1.16 (0.63-2.13)</td>
<td valign="top" align="center">
<break/>
<break/>0.623</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">N stage<break/>&#x2003;N0<break/>&#x2003;N1<break/>&#x2003;N2</td>
<td valign="middle" align="left">
<break/>Reference<break/>2.07 (1.30-3.29)<break/>5.18 (3.02-8.87)</td>
<td valign="middle" align="center">
<break/>
<break/>0.002<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>1.92 (1.16-3.16)<break/>4.57 (2.56-8.15)</td>
<td valign="top" align="center">
<break/>
<break/>0.011<sup>*</sup>
<break/>&lt;0.001<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Lymph node dissection<break/>&#x2003;&lt; 12<break/>&#x2003;&#x2265; 12</td>
<td valign="top" align="left">
<break/>Reference<break/>0.81 (0.51-1.28)</td>
<td valign="top" align="center">
<break/>
<break/>0.370</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Perineural invasion<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.09 (1.01-4.32)</td>
<td valign="top" align="center">
<break/>
<break/>0.047</td>
<td valign="top" align="left">
<break/>Reference<break/>1.85 (0.85-4.02)</td>
<td valign="top" align="center">
<break/>
<break/>0.120</td>
</tr>
<tr>
<td valign="top" align="left">Vessel invasion<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.51 (1.26-4.99)</td>
<td valign="top" align="center">
<break/>
<break/>0.009</td>
<td valign="top" align="left">
<break/>Reference<break/>2.03 (0.97-4.24)</td>
<td valign="top" align="center">
<break/>
<break/>0.059</td>
</tr>
<tr>
<td valign="top" align="left">Chemotherapy<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>0.52 (0.35-0.78)</td>
<td valign="top" align="center">
<break/>
<break/>0.002</td>
<td valign="top" align="left">
<break/>Reference<break/>0.77 (0.47-1.26)</td>
<td valign="top" align="center">
<break/>
<break/>0.300</td>
</tr>
<tr>
<td valign="top" align="left">M-NPS Group<break/>&#x2003;0<break/>&#x2003;1<break/>&#x2003;2</td>
<td valign="top" align="left">
<break/>Reference<break/>2.21 (1.39-3.53)<break/>3.56 (1.92-6.61)</td>
<td valign="top" align="center">
<break/>
<break/>&lt;0.001<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>1.73 (1.05-2.86)<break/>2.55 (1.29-5.03)</td>
<td valign="top" align="center">
<break/>
<break/>0.031<sup>*</sup>
<break/>0.007<sup>*</sup>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>NPS, Naples prognostic score; M-NPS, modified NPS.</p>
</fn>
<fn>
<p>*Statistically significant.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>In addition, the same analytical methods as for OS were executed for CSS (<xref ref-type="table" rid="T4">
<bold>Table&#xa0;4</bold>
</xref>). CSS was notably correlated with the M-NPS group in the univariate analysis. CSS was independently influenced by the M-NPS group in multivariate analysis. Group 2 had worse CSS compared to group 0 [G2 vs G0: 2.52 (1.24&#x2013;5.14)]. Obstruction, gross tumor type, and N stage were also independent prognostic risk parameters of CSS.</p>
<table-wrap id="T4" position="float">
<label>Table&#xa0;4</label>
<caption>
<p>Univariate and multivariate analyses of the prognostic factor for CSS.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" rowspan="2" align="left">Variables</th>
<th valign="top" colspan="2" align="center">Univariate analysis</th>
<th valign="top" colspan="2" align="center">Multivariate analysis</th>
</tr>
<tr>
<th valign="top" align="center">HR (95% CI)</th>
<th valign="top" align="center">
<italic>P</italic>-value</th>
<th valign="top" align="left">HR (95% CI)</th>
<th valign="top" align="center">
<italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age</td>
<td valign="top" align="left">1.03 (1.01-1.05)</td>
<td valign="top" align="center">0.002</td>
<td valign="middle" align="left">1.02 (1.00-1.05)</td>
<td valign="top" align="center">0.052</td>
</tr>
<tr>
<td valign="top" align="left">Sex<break/>&#x2003;Female<break/>&#x2003;Male</td>
<td valign="top" align="left">
<break/>Reference<break/>1.37 (0.88-2.15)</td>
<td valign="top" align="center">
<break/>
<break/>0.166</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Underlying disease<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>1.05 (0.66-1.66,)</td>
<td valign="top" align="center">
<break/>
<break/>0.849</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Anemia<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>0.84 (0.54-1.31)</td>
<td valign="top" align="center">
<break/>
<break/>0.441</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Tumor location<break/>&#x2003;Right hemicolon<break/>&#x2003;Left hemicolon</td>
<td valign="top" align="left">
<break/>Reference<break/>1.05 (0.67-1.63)</td>
<td valign="top" align="center">
<break/>
<break/>0.843</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">ASA<break/>&#x2003;1/2<break/>&#x2003;3/4</td>
<td valign="middle" align="left">
<break/>Reference<break/>1.81 (1.15-2.84)</td>
<td valign="middle" align="center">
<break/>
<break/>0.011</td>
<td valign="top" align="left">
<break/>Reference<break/>1.03 (0.59-1.81)</td>
<td valign="top" align="center">
<break/>
<break/>0.911</td>
</tr>
<tr>
<td valign="top" align="left">Surgical approach<break/>&#x2003;Laparoscopic<break/>&#x2003;Open</td>
<td valign="top" align="left">
<break/>Reference<break/>1.57 (0.97-2.53)</td>
<td valign="top" align="center">
<break/>
<break/>0.067</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Ascites<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="middle" align="left">
<break/>Reference<break/>2.09 (1.26-3.48)</td>
<td valign="middle" align="center">
<break/>
<break/>0.004</td>
<td valign="top" align="left">
<break/>Reference<break/>0.89 (0.48-1.63)</td>
<td valign="top" align="center">
<break/>
<break/>0.706</td>
</tr>
<tr>
<td valign="top" align="left">Intestinal perforation<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.43 (0.77-7.71)</td>
<td valign="top" align="center">
<break/>
<break/>0.132</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Obstruction<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.65 (1.70-4.12)</td>
<td valign="top" align="center">
<break/>
<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>2.38 (1.43-3.96)</td>
<td valign="top" align="center">
<break/>
<break/>0.001<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Tumor size<break/>&#x2003;&#x2264; 5 cm<break/>&#x2003;&gt; 5 cm</td>
<td valign="top" align="left">
<break/>Reference<break/>1.03 (0.66-1.62)</td>
<td valign="top" align="center">
<break/>
<break/>0.887</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Gross tumor type<break/>&#x2003;Infiltrative<break/>&#x2003;Ulcerated<break/>&#x2003;Elevated</td>
<td valign="middle" align="left">
<break/>Reference<break/>0.70 (0.28-1.74)<break/>0.26 (0.09-0.74)</td>
<td valign="middle" align="center">
<break/>
<break/>0.442<break/>0.011</td>
<td valign="top" align="left">
<break/>Reference<break/>0.50 (0.19-1.35)<break/>0.20 (0.06-0.59)</td>
<td valign="top" align="center">
<break/>
<break/>0.170<break/>0.004<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Pathology type<break/>&#x2003;Adenocarcinoma<break/>&#x2003;Mucinous<break/>&#x2003;Mixed</td>
<td valign="top" align="left">
<break/>Reference<break/>0.93 (0.43-2.04)<break/>0.99 (0.45-2.16)</td>
<td valign="top" align="center">
<break/>
<break/>0.864<break/>0.984</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Differentiation<break/>&#x2003;Well<break/>&#x2003;Moderately<break/>&#x2003;Poorly</td>
<td valign="top" align="left">
<break/>Reference<break/>0.91 (0.22-3.71)<break/>0.96 (0.21-4.46)</td>
<td valign="top" align="center">
<break/>
<break/>0.895<break/>0.962</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">T stage<break/>&#x2003;T2 &amp; T3<break/>&#x2003;T4</td>
<td valign="top" align="left">
<break/>Reference<break/>1.34 (0.67-2.69)</td>
<td valign="top" align="center">
<break/>
<break/>0.403</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">N stage<break/>&#x2003;N0<break/>&#x2003;N1<break/>&#x2003;N2</td>
<td valign="middle" align="left">
<break/>Reference<break/>2.15 (1.29-3.58)<break/>6.06 (3.43-10.68)</td>
<td valign="middle" align="center">
<break/>
<break/>0.003<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>1.80 (1.05-3.10)<break/>5.37 (2.91-9.91)</td>
<td valign="top" align="center">
<break/>
<break/>0.034<sup>*</sup>
<break/>&lt;0.001<sup>*</sup>
</td>
</tr>
<tr>
<td valign="top" align="left">Lymph node dissection<break/>&#x2003;&lt; 12<break/>&#x2003;&#x2265; 12</td>
<td valign="top" align="left">
<break/>Reference<break/>0.88 (0.53-1.47)</td>
<td valign="top" align="center">
<break/>
<break/>0.637</td>
<td valign="top" align="left"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Perineural invasion<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.47 (1.19-5.13)</td>
<td valign="top" align="center">
<break/>
<break/>0.016</td>
<td valign="top" align="left">
<break/>Reference<break/>2.05 (0.94-4.48)</td>
<td valign="top" align="center">
<break/>
<break/>0.071</td>
</tr>
<tr>
<td valign="top" align="left">Vessel invasion<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>2.29 (1.05-4.97)</td>
<td valign="top" align="center">
<break/>
<break/>0.037</td>
<td valign="top" align="left">
<break/>Reference<break/>1.98 (0.86-4.52))</td>
<td valign="top" align="center">
<break/>
<break/>0.107</td>
</tr>
<tr>
<td valign="top" align="left">Chemotherapy<break/>&#x2003;No<break/>&#x2003;Yes</td>
<td valign="top" align="left">
<break/>Reference<break/>0.57 (0.37-0.89)</td>
<td valign="top" align="center">
<break/>
<break/>0.014</td>
<td valign="top" align="left">
<break/>Reference<break/>0.73 (0.43-1.25)</td>
<td valign="top" align="center">
<break/>
<break/>0.249</td>
</tr>
<tr>
<td valign="top" align="left">M-NPS Group<break/>&#x2003;0<break/>&#x2003;1<break/>&#x2003;2</td>
<td valign="top" align="left">
<break/>Reference<break/>1.91 (1.16-3.15)<break/>3.35 (1.74-6.44)</td>
<td valign="top" align="center">
<break/>
<break/>0.011<break/>&lt;0.001</td>
<td valign="top" align="left">
<break/>Reference<break/>1.45 (0.85-2.49)<break/>2.52 (1.24-5.14)</td>
<td valign="top" align="center">
<break/>
<break/>0.175<break/>0.011<sup>*</sup>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>NPS, Naples prognostic score; M-NPS, modified NPS.</p>
</fn>
<fn>
<p>*Statistically significant.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3_4">
<title>Division of the dataset and construction of the nomogram</title>
<p>The total of 328 patients finally included were stochastically allocated into two cohorts: 213 in the training set and 115 in the validation set. All clinicopathological characteristics in two sets are listed in <xref ref-type="table" rid="T5">
<bold>Table&#xa0;5</bold>
</xref>. No statistical difference in clinicopathological characteristics between the two cohorts proved that the allocation was completely randomized (<xref ref-type="table" rid="T5">
<bold>Table&#xa0;5</bold>
</xref>).</p>
<table-wrap id="T5" position="float">
<label>Table&#xa0;5</label>
<caption>
<p>Patients&#x2019; clinicopathological characteristics in the training and validation cohort.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Variables</th>
<th valign="middle" align="left">All patients<break/>(n = 328)</th>
<th valign="middle" align="left">Training set<break/>(n = 213)</th>
<th valign="middle" align="left">Validation set<break/>(n = 115)</th>
<th valign="middle" align="left">
<italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left" style="">Age, M (Q&#x2081;, Q&#x2083;)</td>
<td valign="middle" align="left" style="">62.00 (52, 72)</td>
<td valign="middle" align="left" style="">62.00 (52, 71)</td>
<td valign="middle" align="left" style="">62.00 (53, 74)</td>
<td valign="middle" align="left" style="">0.306</td>
</tr>
<tr>
<td valign="middle" align="left" style="">Sex, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.790</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Female</td>
<td valign="middle" align="left" style="">163 (49.70)</td>
<td valign="middle" align="left" style="">107 (50.23)</td>
<td valign="middle" align="left" style="">56 (48.70)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Male</td>
<td valign="middle" align="left" style="">165 (50.30)</td>
<td valign="middle" align="left" style="">106 (49.77)</td>
<td valign="middle" align="left" style="">59 (51.30)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Underlying disease, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.378</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">215 (65.55)</td>
<td valign="middle" align="left" style="">136 (63.85)</td>
<td valign="middle" align="left" style="">79 (68.70)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">113 (34.45)</td>
<td valign="middle" align="left" style="">77 (36.15)</td>
<td valign="middle" align="left" style="">36 (31.30)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Anemia, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.241</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">134 (40.85)</td>
<td valign="middle" align="left" style="">92 (43.19)</td>
<td valign="middle" align="left" style="">42 (36.52)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">194 (59.15)</td>
<td valign="middle" align="left" style="">121 (56.81)</td>
<td valign="middle" align="left" style="">73 (63.48)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Tumor location, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.980</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Right hemicolon</td>
<td valign="middle" align="left" style="">180 (54.88)</td>
<td valign="middle" align="left" style="">117 (54.93)</td>
<td valign="middle" align="left" style="">63 (54.78)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Left hemicolon</td>
<td valign="middle" align="left" style="">148 (45.12)</td>
<td valign="middle" align="left" style="">96 (45.07)</td>
<td valign="middle" align="left" style="">52 (45.22)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">ASA, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.790</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;1/2</td>
<td valign="middle" align="left" style="">234 (71.34)</td>
<td valign="middle" align="left" style="">153 (71.83)</td>
<td valign="middle" align="left" style="">81 (70.43)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;3/4</td>
<td valign="middle" align="left" style="">94 (28.66)</td>
<td valign="middle" align="left" style="">60 (28.17)</td>
<td valign="middle" align="left" style="">34 (29.57)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Surgical approach, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.855</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Open</td>
<td valign="middle" align="left" style="">199 (60.67)</td>
<td valign="middle" align="left" style="">130 (61.03)</td>
<td valign="middle" align="left" style="">69 (60.00)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Laparoscopic</td>
<td valign="middle" align="left" style="">129 (39.33)</td>
<td valign="middle" align="left" style="">83 (38.97)</td>
<td valign="middle" align="left" style="">46 (40.00)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Ascites, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.941</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">276 (84.15)</td>
<td valign="middle" align="left" style="">179 (84.04)</td>
<td valign="middle" align="left" style="">97 (84.35)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">52 (15.85)</td>
<td valign="middle" align="left" style="">34 (15.96)</td>
<td valign="middle" align="left" style="">18 (15.65)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Intestinal perforation, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.971</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">321 (97.87)</td>
<td valign="middle" align="left" style="">209 (98.12)</td>
<td valign="middle" align="left" style="">112 (97.39)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">7 (2.13)</td>
<td valign="middle" align="left" style="">4 (1.88)</td>
<td valign="middle" align="left" style="">3 (2.61)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Obstruction, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.390</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">221 (67.38)</td>
<td valign="middle" align="left" style="">147 (69.01)</td>
<td valign="middle" align="left" style="">74 (64.35)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">107 (32.62)</td>
<td valign="middle" align="left" style="">66 (30.99)</td>
<td valign="middle" align="left" style="">41 (35.65)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Tumor size, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.103</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;&gt;5</td>
<td valign="middle" align="left" style="">128 (39.02)</td>
<td valign="middle" align="left" style="">90 (42.25)</td>
<td valign="middle" align="left" style="">38 (33.04)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;&#x2264;5</td>
<td valign="middle" align="left" style="">200 (60.98)</td>
<td valign="middle" align="left" style="">123 (57.75)</td>
<td valign="middle" align="left" style="">77 (66.96)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Gross tumor type, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.460</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Elevated</td>
<td valign="middle" align="left" style="">94 (28.66)</td>
<td valign="middle" align="left" style="">63 (29.58)</td>
<td valign="middle" align="left" style="">31 (26.96)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Infiltrative</td>
<td valign="middle" align="left" style="">14 (4.27)</td>
<td valign="middle" align="left" style="">7 (3.29)</td>
<td valign="middle" align="left" style="">7 (6.09)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Ulcerated</td>
<td valign="middle" align="left" style="">220 (67.07)</td>
<td valign="middle" align="left" style="">143 (67.14)</td>
<td valign="middle" align="left" style="">77 (66.96)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Pathology type, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.958</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Adenocarcinoma</td>
<td valign="middle" align="left" style="">271 (82.62)</td>
<td valign="middle" align="left" style="">176 (82.63)</td>
<td valign="middle" align="left" style="">95 (82.61)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Mixed</td>
<td valign="middle" align="left" style="">27 (8.23)</td>
<td valign="middle" align="left" style="">17 (7.98)</td>
<td valign="middle" align="left" style="">10 (8.70)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Mucinous adenocarcinomas</td>
<td valign="middle" align="left" style="">30 (9.15)</td>
<td valign="middle" align="left" style="">20 (9.39)</td>
<td valign="middle" align="left" style="">10 (8.70)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Differentiation, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.931</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Moderately</td>
<td valign="middle" align="left" style="">283 (86.28)</td>
<td valign="middle" align="left" style="">183 (85.92)</td>
<td valign="middle" align="left" style="">100 (86.96)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Poorly</td>
<td valign="middle" align="left" style="">37 (11.28)</td>
<td valign="middle" align="left" style="">25 (11.74)</td>
<td valign="middle" align="left" style="">12 (10.43)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Well</td>
<td valign="middle" align="left" style="">8 (2.44)</td>
<td valign="middle" align="left" style="">5 (2.35)</td>
<td valign="middle" align="left" style="">3 (2.61)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">T stage, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.245</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;T2/T3</td>
<td valign="middle" align="left" style="">47 (14.33)</td>
<td valign="middle" align="left" style="">27 (12.68)</td>
<td valign="middle" align="left" style="">20 (17.39)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;T4</td>
<td valign="middle" align="left" style="">281 (85.67)</td>
<td valign="middle" align="left" style="">186 (87.32)</td>
<td valign="middle" align="left" style="">95 (82.61)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">N stage, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.128</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;N0</td>
<td valign="middle" align="left" style="">207 (63.11)</td>
<td valign="middle" align="left" style="">134 (62.91)</td>
<td valign="middle" align="left" style="">73 (63.48)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;N1</td>
<td valign="middle" align="left" style="">91 (27.74)</td>
<td valign="middle" align="left" style="">64 (30.05)</td>
<td valign="middle" align="left" style="">27 (23.48)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;N2</td>
<td valign="middle" align="left" style="">30 (9.15)</td>
<td valign="middle" align="left" style="">15 (7.04)</td>
<td valign="middle" align="left" style="">15 (13.04)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Lymph Nodes, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.519</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;&lt;12</td>
<td valign="middle" align="left" style="">76 (23.17)</td>
<td valign="middle" align="left" style="">47 (22.07)</td>
<td valign="middle" align="left" style="">29 (25.22)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;&#x2265;12</td>
<td valign="middle" align="left" style="">252 (76.83)</td>
<td valign="middle" align="left" style="">166 (77.93)</td>
<td valign="middle" align="left" style="">86 (74.78)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Perineural Invasion1, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.240</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">310 (94.51)</td>
<td valign="middle" align="left" style="">199 (93.43)</td>
<td valign="middle" align="left" style="">111 (96.52)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">18 (5.49)</td>
<td valign="middle" align="left" style="">14 (6.57)</td>
<td valign="middle" align="left" style="">4 (3.48)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Vessel invasion1, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.587</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">311 (94.82)</td>
<td valign="middle" align="left" style="">203 (95.31)</td>
<td valign="middle" align="left" style="">108 (93.91)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">17 (5.18)</td>
<td valign="middle" align="left" style="">10 (4.69)</td>
<td valign="middle" align="left" style="">7 (6.09)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">Chemotherapy, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.366</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;No</td>
<td valign="middle" align="left" style="">122 (37.20)</td>
<td valign="middle" align="left" style="">83 (38.97)</td>
<td valign="middle" align="left" style="">39 (33.91)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;Yes</td>
<td valign="middle" align="left" style="">206 (62.80)</td>
<td valign="middle" align="left" style="">130 (61.03)</td>
<td valign="middle" align="left" style="">76 (66.09)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">M-NPS group, n (%)</td>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style=""/>
<td valign="middle" align="left" style="">0.121</td>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;G0</td>
<td valign="middle" align="left" style="">153 (46.65)</td>
<td valign="middle" align="left" style="">101 (47.42)</td>
<td valign="middle" align="left" style="">52 (45.22)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;G1</td>
<td valign="middle" align="left" style="">145 (44.21)</td>
<td valign="middle" align="left" style="">88 (41.31)</td>
<td valign="middle" align="left" style="">57 (49.57)</td>
<td valign="middle" align="left" style=""/>
</tr>
<tr>
<td valign="middle" align="left" style="">&#x2003;G2</td>
<td valign="middle" align="left" style="">30 (9.15)</td>
<td valign="middle" align="left" style="">24 (11.27)</td>
<td valign="middle" align="left" style="">6 (5.22)</td>
<td valign="middle" align="left" style=""/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>M, Median, Q&#x2081;, 1st Quartile, Q&#x2083;, 3st Quartile; M-NPS, modified Naples prognostic score.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>OS and CSS nomograms were created to forecast the survival rates at 3, 5, and 10 years, using independent parameters that influence OS and CSS, respectively (<xref ref-type="fig" rid="f4">
<bold>Figure&#xa0;4</bold>
</xref>). Nomograms can personalize the forecast of OS and CSS for each patient by calculating the sum of the corresponding score for each variable in the models.</p>
<fig id="f4" position="float">
<label>Figure&#xa0;4</label>
<caption>
<p>Nomograms for OS and CSS. <bold>(A)</bold> Nomogram for predicting 3-, 5- and 10-year OS. <bold>(B)</bold> Nomogram for predicting 3-, 5- and 10-year CSS. OS, overall survival; CSS, cancer-specific survival.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g004.tif"/>
</fig>
</sec>
<sec id="s3_5">
<title>Evaluation of nomogram prediction models</title>
<p>The C-indexes for OS and CSS nomograms in the training cohort were 0.802 (0.747&#x2013;0.857) and 0.783 (0.722&#x2013;0.844), respectively. In the validation cohort, the C-indexes for OS and CSS nomograms were 0.742 (0.656&#x2013;0.828) and 0.745 (0.649&#x2013;0.841), respectively.</p>
<p>ROC analysis indicated that the nomogram for OS in the training cohort achieved AUC values of 0.82, 0.82, and 0.87 for the 3-, 5-, and 10-year predictions, respectively (<xref ref-type="fig" rid="f5">
<bold>Figure&#xa0;5A</bold>
</xref>). In the validation cohort, the predictive model for OS reached AUC values of 0.75, 0.77, and 0.82, respectively (<xref ref-type="fig" rid="f5">
<bold>Figure&#xa0;5B</bold>
</xref>). The nomogram&#x2019;s calibration curves demonstrated that excellent alignment between predicted and actual 3-, 5-, and 10-year OS in both the training (<xref ref-type="fig" rid="f5">
<bold>Figure&#xa0;5C</bold>
</xref>) and validation sets (<xref ref-type="fig" rid="f5">
<bold>Figure&#xa0;5D</bold>
</xref>). In addition, DCA curves showed that the predictive model of OS had excellent clinical efficacy at 3, 5, and 10 years in clinical practice (<xref ref-type="fig" rid="f5">
<bold>Figures&#xa0;5E, F</bold>
</xref>).</p>
<fig id="f5" position="float">
<label>Figure&#xa0;5</label>
<caption>
<p>Evaluation of the nomogram of OS. ROC curves of nomograms for 3-, 5- and 10-year OS in the training <bold>(A)</bold> and validation cohort <bold>(B)</bold>. Calibration curves of the nomogram for the probability of 3-, 5- and 10-year OS in the training <bold>(C)</bold> and validation cohort <bold>(D)</bold>. DCA curves of the nomogram for 3-, 5- and 10-year OS in the training <bold>(E)</bold> and validation cohort <bold>(F)</bold>. OS, overall survival.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g005.tif"/>
</fig>
<p>At the same time, the CSS nomogram in the training set attained AUC values of 0.81, 0.80, and 0.80 for the 3-, 5-, and 10-year predictions, respectively (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6A</bold>
</xref>). In the validation set, the CSS nomogram got AUC values of 0.73, 0.75, and 0.80 for the 3-, 5-, and 10-year predictions, respectively (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6B</bold>
</xref>). In the training (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6C</bold>
</xref>) and validation cohort (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6D</bold>
</xref>), the nomogram&#x2019;s calibration curves exhibited an excellent level of consistency between the model-forecasted CSS and the actual survival outcomes. Additionally, DCA curves for the nomogram of CSS indicated that the model had favorable clinical efficacy in both the training (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6E</bold>
</xref>) and validation cohort (<xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6F</bold>
</xref>).</p>
<fig id="f6" position="float">
<label>Figure&#xa0;6</label>
<caption>
<p>Evaluation of the nomogram of CSS. ROC curves of nomograms for 3-, 5- and 10-year CSS in the training <bold>(A)</bold> and validation cohort <bold>(B)</bold>. Calibration curves of the nomogram for the probability of 3-, 5- and 10-year CSS in the training <bold>(C)</bold> and validation cohort <bold>(D)</bold>. DCA curves for training <bold>(E)</bold> and validation cohort <bold>(F)</bold> at 3-, 5-, and 10-year CSS. CSS, cancer-specific survival.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1403666-g006.tif"/>
</fig>
</sec>
</sec>
<sec id="s4" sec-type="discussion">
<title>Discussion</title>
<p>Recently, research has been conducted extensively on the application of NPS to predict the outcome of numerous types of cancer due to the integration of multiple indicators of nutritional, inflammatory, and immune status (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B30">30</xref>, <xref ref-type="bibr" rid="B34">34</xref>&#x2013;<xref ref-type="bibr" rid="B36">36</xref>). NPS thresholds in different cancer types and treatment contexts remain controversial. In our research, the X-Tile was employed to construct M-NPS based on stage II-III patients in the research center. Furthermore, we examined the connection between M-NPS and patients&#x2019; clinicopathological parameters and assessed the predictive significance of M-NPS for OS and CSS. Finally, OS and CSS nomograms containing M-NPS are established and validated.</p>
<p>NLR is a highly reliable indicator of systemic inflammation. The threshold value for NLR in NPS was originally defined by Gennaro et&#xa0;al. (<xref ref-type="bibr" rid="B30">30</xref>) as 4.44, and the cutoff value identified in this study was very close to 4.04. LMR is used as a marker of the host&#x2019;s immunological response. We determined a cutoff value of 1.72 for LMR, however, the cutoff value for LMR in NPS is 2.96. In addition, the cutoff values for ALB and CHOL levels, which represent nutritional status, also differed from those defined by Gennaro et&#xa0;al. (<xref ref-type="bibr" rid="B30">30</xref>). The above differences may originate from the race, lifestyle, and dietary structure of Eastern and Western populations.</p>
<p>Accumulating evidence suggests that patients with CRC in a hyperinflammatory state portend an unfavorable prognosis, whereas patients in a good nutritional state show longer survival (<xref ref-type="bibr" rid="B15">15</xref>). Our study showed that colon cancer patients with low NLR, high ALB and high CHOL had a more favorable survival compared to those with high NLR, low ALB and low CHOL. Therefore, as recommended by the guidelines (<xref ref-type="bibr" rid="B37">37</xref>), an appropriate anti-inflammatory and nutritious diet is crucial in preventing the occurrence of colon cancer and reducing postoperative colon cancer deaths.</p>
<p>Our study revealed that obstruction was a significant predictive indicator for OS and CSS in stage II-III patients. Relevant studies have pointed out that obstruction as a marker of malignancy portends an unfavorable prognosis in CRC patients even after radical surgery (<xref ref-type="bibr" rid="B38">38</xref>&#x2013;<xref ref-type="bibr" rid="B40">40</xref>). Obstruction causes dysbiosis and increased toxins, resulting in local and systemic inflammatory responses to remodel the tumor microenvironment (<xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B42">42</xref>). Inflammation associated with cancer not only facilitates the growth of malignant tumors but can also reduce response to chemotherapeutic agents by inducing genetic instability (<xref ref-type="bibr" rid="B43">43</xref>). We have also found in the study that the gross tumor type was also an independent prognostic factor for the prognosis of patients with stage II-III colon cancer. As we all know, the gross tumor type reflects the biology of the cancer itself. Infiltrative colon cancers are the most malignant and elevated colon cancers are the least malignant. Previous studies have also revealed that gross tumor type could serve as a marker of survival and peritoneal metastasis in CRC (<xref ref-type="bibr" rid="B44">44</xref>, <xref ref-type="bibr" rid="B45">45</xref>), which is consistent with our results.</p>
<p>NPS, as a novel and powerful scoring system, has been widely applied in the construction of prognostic nomograms for a variety of cancers, including gastric cancer (<xref ref-type="bibr" rid="B46">46</xref>), small cell lung cancer (<xref ref-type="bibr" rid="B47">47</xref>), esophageal squamous cell carcinoma (<xref ref-type="bibr" rid="B48">48</xref>, <xref ref-type="bibr" rid="B49">49</xref>), cholangiocarcinoma (<xref ref-type="bibr" rid="B50">50</xref>), gallbladder cancer (<xref ref-type="bibr" rid="B51">51</xref>) and osteosarcoma (<xref ref-type="bibr" rid="B52">52</xref>). Currently, there are no reports related to the application of NPS to the prognostic nomogram of colon cancer. For the first time, we incorporated M-NPS into the predictive nomogram for colon cancer patients in stages II&#x2013;III. Nomograms integrating M-NPS exhibited excellent predictive ability for 3, 5, and 10-year OS or CSS.</p>
<p>This study relies on a national clinical key specialty platform with a superb surgical team, sufficient surgical patients and advanced instrumentation. In addition, the professional follow-up process provides a strong warrant for the reliability of the study&#x2019;s conclusions. However, there exist some constraints in our research. Initially, the retrospective study is susceptible to selection bias. Besides, the sample size of a single center is relatively limited and the number of outcome events is relatively few. Hence, the clinical significance of M-NPS has to be validated through prospective multicenter trials involving a substantial number of participants.</p>
</sec>
<sec id="s5" sec-type="conclusions">
<title>Conclusions</title>
<p>Taken together, M-NPS is a robust survival predictor in curative stage II-III patients. Nomograms incorporating M-NPS for OS and CSS have good predictive performance and clinical utility.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability">
<title>Data availability statement</title>
<p>The data used in the study are not publicly available due to privacy restrictions but are available from the corresponding author on reasonable request.</p>
</sec>
<sec id="s7" sec-type="ethics-statement">
<title>Ethics statement</title>
<p>The studies involving humans were approved by the Ethics Committee of the First Affiliated Hospital of Xi&#x2019;an Jiaotong University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. This study is a clinical study and did not involve the ethics of animal and cellular experiments.</p>
</sec>
<sec id="s8" sec-type="author-contributions">
<title>Author contributions</title>
<p>XL: Writing &#x2013; original draft, Formal analysis. CC: Data curation, Writing &#x2013; review &amp; editing. XH: Project administration, Writing &#x2013; review &amp; editing. CZ: Data curation, Formal analysis, Writing &#x2013; review &amp; editing. HY: Formal analysis, Visualization, Writing &#x2013; review &amp; editing. GC: Formal analysis, Visualization, Writing &#x2013; review &amp; editing. JY: Formal analysis, Visualization, Writing &#x2013; review &amp; editing. MM: Project administration, Supervision, Writing &#x2013; review &amp; editing. XS: Funding acquisition, Project administration, Supervision, Writing &#x2013; review &amp; editing.</p>
</sec>
<sec id="s9" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Natural Science Foundation of China (Grant No. 81972720). This study was funded by the IIT Project of the First Affiliated Hospital of Xi'an Jiaotong University (Grant No: XJTU1AF-CRF-2024-012).</p>
</sec>
<ack>
<title>Acknowledgments</title>
<p>We would like to thank CC for his great contribution to the prognostic follow-up of colon cancer cases.</p>
</ack>
<sec id="s10" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s11" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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