Gliomas are the most common primary malignant brain tumors in adults, which can occur anywhere in the central nervous system but primarily occur in the brain and originate in the glial tissue (1). Glioblastoma (GBM), the World Health Organization (WHO) grade 4 glioma, accounts for approximately 80% of malignant gliomas and is characterized by considerable cellularity and mitotic activity, vascular proliferation, and necrosis (2). The median overall survival (OS) is about 15 months in patients with this incurable disease, even after receiving standardized radiotherapy and temozolomide (TMZ), and there also remains a very high risk of recurrence (3). Despite considerable effort, little progress has been made toward prolonged survival in GBM (4).

In 1863, Rudolf Virchow firstly introduced the concept “inflammation and cancer” based on the observation on leukocytes in neoplastic tissues (5). In recent years, researchers have found that inflammation plays a crucial role in tumorigenesis, which is also considered as a hallmark feature of cancer development and progression (6–8). Systemic inflammatory response, mainly produced by peripheral immune cells, could indirectly reflect the severity of local malignancy. Peripheral blood neutrophil, lymphocyte, monocyte, and platelet are widely used as systemic inflammatory markers for predicting prognosis and evaluating therapeutic response of tumors (9–11). Nutrition is also proposed to play an essential role in cancer progression based on the principle that it can also cause oxidative stress, augment a cascade of molecular reactions in cells, and alter the metabolic state of tissues (12, 13). Patients with wasting diseases like malignancies usually have weak physical conditions. Nutritional markers like albumin, hemoglobin, and BMI have been proven to be effective predictive indicators for disease progression and play a prognostic role (14, 15).

Naples prognostic score (NPS), based on inflammatory markers and nutritional status, was firstly introduced in the research of colorectal cancer by Galizia et al. (16) So far, the prognostic significance has been validated in various cancers (17–20). Controlling nutritional status (CONUT) score is also a useful nutritional marker to evaluate nutritional status and predict prognosis in cancer patients, which is similar in composition with NPS (21–23). Recent studies have reported that both preoperative and postoperative CONUT score serve as an independent prognostic indicator for GBM patients (24, 25). In the current study, we aim to explore the prognostic value of preoperative NPS in GBM patients and compare the prognostic ability between NPS and CONUT.

In recent years, NPS has been widely researched in patients with malignancies, such as colorectal cancer, pancreatic cancer, endometrial cancer, lung cancer, gastric cancer, and esophageal squamous cell carcinoma (18–20, 28–30). These studies have found that preoperative NPS served as a reliable indicator to effectively predict prognosis mainly including OS and progression-free survival (PFS). In the current study, we attempt to explore the prognostic significance of preoperative NPS in newly diagnosed GBM patients. The results from our research are consistent with previous research, which indicates that NPS is an independent prognostic predictor.

Inflammation and malnutrition are basic characteristics for patients with malignancies. Tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Many cancers arise from sites of infection, chronic irritation, and inflammation (8, 31). Changes in systemic inflammation could reflect the progression of local inflammation in tumors or adjacent to tumors; thus, researchers use peripheral blood immune cells to evaluate the progression of disease. In fact, these methods are also applied in patients with chronic medical disease such as coronary heart disease, systemic lupus erythematosus, and end-stage renal disease (32–34). The representative blood inflammatory markers mainly include leukocyte, neutrophil, lymphocyte, platelet, monocyte, and their combinations like neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio, which have been widely used in estimating conditions of diseases.

Nutrition status plays different roles in tumorigenesis and disease progression. On the one hand, nutrition and dietary factors have been associated with cancer risk. Nutrition/dietary components are likely to have an effect on an individual’s risk of cancer and that the mechanism by which cancer risk is affected is likely to be through epigenetic modification of an individual’s genome (35, 36). On the other hand, endless growth of malignancies has a tendency to deplete nutrients and leads to malnutrition conditions, and malnutrition can impact disease progression and survival in cancer patients (37). Various peripheral blood nutritional parameters have been reported to be associated with prognosis in patients with different malignancies. Among these markers, serum albumin concentrate and prognostic nutritional index (PNI) that contains albumin and lymphocyte have been used frequently (38–40). High concentration of nutritional markers, which indicates better nutritional status, usually relates to favorable prognosis. Cholesterol is an uncommon nutritional marker and is vital for the survival and growth of mammalian cells. It has been reported that cholesterol concentrate is significantly correlated with the incidence and progression of various malignancies like prostate cancer and breast cancer (41–44). As an indicator of nutrition, however, high cholesterol concentrate usually has been associated with favorable prognosis in cancer patients (45–47).

There has been a close relationship between systemic inflammatory response and nutrition (48). Nutritional status affects circulating immune cells, especially T cells, in population, metabolism, and function; hence abnormal nutritional conditions would break the balance of systemic inflammation (49). The combination of systemic inflammatory markers and nutritional markers to predict prognosis and progression of disease has been widely used and proved to be useful, and the representatives include Glasgow prognostic score (GPS), CONUT, and NPS (16, 21, 50). Other different combinations of two kinds of markers are also determined to have effective prognostic ability in tumors (51, 52). Some of these prognostic scores like GPS and CONUT are also researched in patients with GBM, and the results are consistent with those of previous studies (25, 53).

There are still some limitations in our research. First, it is a single-center retrospective clinical research, and multi-center collaborations and prospective experimental design are needed to verify the results. Second, it is hard for us to build a validation cohort due to the relatively small sample size. Third, patients lost to follow-up may cause selection bias in analysis. Fourth, some important glioma-related biomarkers like O6-methylguanine-DNA methyltransferase (MGMT) methylation and telomerase reverse transcriptase (TERT) mutation status were not included in the study due to incomplete pathological information.

To our knowledge, this is the first study to evaluate the prognostic role of preoperative NPS in newly diagnosed GBM patients. In the current study, we find NPS as an independent prognostic indicator for patients with newly diagnosed GBM patients, and the prognostic ability of NPS is superior to a similar prognostic score, CONUT. This easily acquired preoperative prognostic score has the potential to be used in clinical work, and will be verified in future research.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Sichuan University. The patients/participants provided their written informed consent to participate in this study.

Conception and design: YL, JL, and WY. Provision of study materials or patients: JL, YY, and TL. Collection and assembly of data: MZ, ZW, and WY. Data analysis and interpretation: JL and YY. Manuscript writing: All authors. Final approval of manuscript: All authors.

This study was supported by the Key Research and Development Item from the Department of Science and Technology of Sichuan Province, China (No. 2017SZ0006).

We would like to express our gratitude to all the colleagues who have assisted clinical data collection. We would like to thank all the glioma patients who were admitted in our hospital who have contributed to the development of medicine.

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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