Pancreatic cancer is the seventh most deadly cancer worldwide (1). In 2018, there were 458,918 new cases of pancreatic cancer and 432,242 deaths (1). Pancreatic cancer has a high mortality rate. Although the diagnosis and treatment of pancreatic cancer have greatly advanced over the last several decades, its prognosis remains dismal (2). The 5-year survival rate for all stages of pancreatic cancer is 4.2% (3). The prognosis for patients with metastatic disease is poor, with a 5-year survival rate of 17.4% for patients who undergo surgical resection and only 0.9% for patients who do not undergo resection (3). Therefore, identification of novel and cost-effective biomarkers that can predict the prognosis of patients with pancreatic cancer and provide guidance for individualized treatment is urgently needed.

Increasing evidence has shown that the nutritional status and inflammatory status of the patient play pivotal roles in the development and progression of cancer (4). Many nutritional assessment biomarkers, including the C-reactive protein-to-albumin ratio (5), prognostic nutritional index (6), albumin-to-globulin ratio (7), modified Glasgow prognostic score (8), and the Controlling Nutritional Status (CONUT) score, have been used to predict the prognosis of patients with pancreatic cancer (9, 10). In 2005, Ignacio de Ulíbarri first proposed CONUT and used it to evaluate the nutritional status of patients (11). The calculation of the CONUT score is based on serum albumin, total lymphocyte count, and total cholesterol level (11). The CONUT scoring system is shown in Table 1 ; the score ranges from 0 to 12. The nutritional status of patients with CONUT scores of 0–1, 2–4, 5–8, and 9–12 is normal, light, moderate, and severe, respectively. The higher the CONUT score, the worse the nutritional status. Many studies have investigated the prognostic role of the CONUT score for patients with pancreatic cancer; however, the results of these studies were inconsistent (9, 10, 12–16). Therefore, we performed this meta-analysis to investigate the prognostic and clinicopathological significance of the CONUT score for patients with pancreatic cancer.

In recent years, the prognostic value of inflammatory and nutritional indices of patients with cancer has been extensively investigated (19–21). Studies have investigated the prognostic value of the CONUT score for patients with pancreatic cancer, but the results were inconsistent. In our meta-analysis, we combined data from seven studies that comprised 2,294 patients. The pooled data demonstrated that a high CONUT score was a significant prognostic biomarker for predicting the OS but not the RFS of patients with pancreatic cancer. Additionally, an elevated CONUT score correlated with male patients with pancreatic cancer, which suggests that male patients with pancreatic cancer tend to have higher CONUT scores. Thus, a high CONUT score was a reliable prognostic factor for a poor OS for patients with pancreatic cancer and could be used to identify high-risk patients. To our knowledge, this meta-analysis was the first to investigate the prognostic value of the CONUT score of patients with pancreatic cancer.

The CONUT score was computed using serum albumin, total lymphocyte count, and total cholesterol values. Patients with low levels of these parameters have a low CONUT score. The biological mechanisms involved in the prognostic value of the CONUT score with respect to a poor OS for patients with pancreatic cancer are still not fully understood but could be explained by the following points. First, the serum albumin level is an important indicator of nutritional status and is regarded as an acute-phase protein that has a role in systemic inflammation (22). Pretreatment hypoalbuminemia correlates with poor survival of patients with cancer (23). Second, lymphocytes play a pivotal role in cell-mediated antitumor immune responses (24). Tumor-infiltrating lymphocytes are important components of antitumor activity and can induce cytotoxic cell death and inhibit tumor cell proliferation (25). Therefore, low lymphocyte counts can weaken immune responses and lead to poor survival for patients with cancer (26). Third, cholesterol is essential for the maintenance of cell membrane function, which is crucial for signal transduction. Decreased levels of cholesterol can affect the antitumor activity of immunocompetent cells (27). Therefore, a low CONUT score could represent a combination of a low serum albumin level, a low lymphocyte count, and a low total cholesterol level, which is reasonably associated with poor survival in patients with cancer.

Many recent meta-analysis studies also have investigated the prognostic role of the CONUT score with respect to solid tumors. In a meta-analysis that included 3,029 patients, Peng et al. showed that a high CONUT score positively correlated with poor prognoses in patients with non-small cell lung cancer (28). Another meta-analysis of six studies demonstrated that a high CONUT score correlated with a poor OS, cancer-specific survival, and DFS in patients with upper tract urothelial carcinoma or renal cell carcinoma undergoing nephrectomy (29). A meta-analysis by Takagi et al. showed that the preoperative CONUT score was an independent prognostic indicator of survival in patients with gastric cancer (30). Our meta-analysis investigated the prognostic efficiency of the CONUT score for patients with pancreatic cancer. We identified a positive association between the CONUT score and the OS of patients with pancreatic cancer, whereas its prognostic role with respect to the RFS was not significant, maybe because of the relatively short follow-up period for RFS analysis and the small sample size (only five studies were included in the RFS analysis). The prognostic value of the CONUT score for predicting the RFS in pancreatic cancer should be verified by future large-scale trials.

This meta-analysis has several limitations. First, the sample size was relatively small. Only seven studies with 2,294 patients were included in the analysis. The small sample size may have introduced a selection bias in this meta-analysis because when the sample size is small, the data of each individual could have a greater impact on the overall results than when the sample size is larger (31). Second, all included studies were conducted in Asian countries, namely, Japan and China. Although we thoroughly searched the literature, no studies of non-Asian patients met our inclusion criteria. Third, the included studies did not have the same cutoff CONUT scores; four studies used ≥3, two studies used ≥4, and one study used ≥2. The different cutoff CONUT scores may have caused the heterogeneity among the studies.

In summary, our meta-analysis showed that a high CONUT score is significantly associated with a poor OS for patients with pancreatic cancer. Male patients with pancreatic cancer tend to have a higher CONUT score. The CONUT score may be an effective prognostic factor in pancreatic cancer in clinical practice.

All datasets generated for this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

XM and WZ collected, extracted, and performed the quality assessment and analyzed the data; YS conceived and designed this study and wrote the paper. All authors reviewed the final manuscript. All authors contributed to the article and approved the submitted version.

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.

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