In this clinical research, a retrospective study was conducted with 142 GBM patients to assess the prognostic effects of ADS. The results indicated that high AFR (≥ 13.9) was associated with favorable prognosis and patients with high dNLR (≥ 3.3) or ADS (≥ 1) was correlated with poor clinical outcome. Furthermore, ADS is better than the individual markers dNLR or AFR in predicting prognosis of GBM patients. To our knowledge, this is the first study to explore the predictive role of ADS in patients with GBM.
There is growing evidence indicated that inflammatory response-associated with cancer may promote tumor progression . Chemokines and cytokines of tumor cells or host cells regulate cellular communication in the tumor microenvironment, which leads to tumor invasion, metastatic spread, and angiogenesis . It has been reported that inflammatory markers such as PLR and NLR are related to the survival of glioma patients [8, 9]. Also, nutritional status and blood coagulation affect the clinical outcome of GBM patients [10, 11, 14]. ADS represented the inflammation, nutritional information, and blood coagulation of patients, and can be used to assess the survival of GBM patients.
Although previous studies have suggested that dNLR is a noninvasive biomarker for differentiating GBM from low-grade gliomas , few studies have evaluated the role of dNLR in the survival of GBM patients. Unlike NLR, dNLR was calculated by neutrophil count/ (leukocyte count- neutrophil count). Many published studies have reported the prognostic effect of dNLR in cancer patients. Their findings have shown that high dNLR is associated with poor prognosis in patients with lymphoma, pancreatic cancer, gastric cancer, lung cancer, urothelial carcinoma, renal cell carcinoma, hepatocellular carcinoma and colorectal cancer [15–21], which is consistent with our results that GBM patients with increased dNLR have a poor prognosis. Neutrophils are the most abundant white blood cells and play a vital role in inflammatory responses. High dNLR may be due to increased neutrophils or decreased lymphocytes. During the development of GBM, tumor cells release a granulocyte colony-stimulating factor (CSF) to promote the growth of neutrophils, which may promote neutrophil aggregation in glioma. Neutrophil activation associated with glioma may improve tumor growth, immunosuppression, and production of reactive oxygen species . Lymphocyte counts and function were inhibited by tumor-related factors , which reduced lymphocyte resistance to glioma. Therefore, it is not difficult to understand that patients with low dNLR in GBM have a longer survival time than patients with high dNLR.
In addition to nutritional status, serum albumin also represents an inflammatory response . Accumulated evidence suggests that albumin can inhibit IL-6 through TNF-α, and they may be associated with a meditation on anti-cytotoxicity causing immune cells in GBM patients . High albumin is associated with favorable prognosis in patients with GBM . In this study, there was a correlation between albumin and OS in univariate analysis, but there was no statistical significance in the multivariate analysis after adjusting for other factors. The abnormalities of blood coagulation always developed in many cancers, including GBM [28, 29]. Fibrinogen reflects the coagulation status of blood, but the exact cause of the relationship between fibrinogen and tumor growth remained unknown. In recent years, many studies have shown that fibrinogen promotes cell adhesion and proliferation by combining growth factors such as vascular endothelial growth factor and fibroblast growth factor- 2 [30, 31]. Furthermore, fibrinogen can inhibit the natural killer cytotoxicity of tumor cells . Studies have shown that fibrinogen is an independent predictor of survival in patients with non-small cell lung cancer, ovarian cancer and glioma [33–35], which is consistent with our findings that high fibrinogen is associated with poor prognosis. AFR base on the albumin/fibrinogen has also been reported as a prognostic factor associated with survival time of various malignancies . In this study, we also observed that increased AFR is a predictor of favorable prognosis in GBM patients, which is an essential factor consistent with previously published researches .
ADS is a new inflammation-based prognostic score composed of serum albumin, fibrinogen, AFR, and dNLR, which was reported to be related to the survival of ESCC patients . Recently, Gao and her colleagues conducted a clinical study of 153 patients with ESCC, which showed that low ADS was associated with favorable clinical outcomes. The author also suggested that ADS was superior to albumin, fibrinogen, AFR or dNLR in predicting OS in ESCC patients. In the present study, we found that ADS is positively correlated with age, but not with tumor size. The OS of patients with ADS of 1, 2 and 3 is shorter than patients with ADS of 0, which is consistent with previous studies . In addition, ADS is better than the individual markers dNLR or AFR in predicting prognosis of GBM patients. Therefore, it is feasible and straightforward to apply ADS to predict the survival time of GBM patients in the clinic.
However, some limitations of the present study should be noted. On the one hand, some selection bias may be existed in this study due to the nature of the retrospective study. On the other hand, we were unable to assess the postoperative ADS dynamic in GBM patients and the relationship between these dynamics and clinical outcomes. Therefore, future large-samples prospective studies should expend our findings and evaluate the role of dynamic changes in postoperative ADS in GBM patients.