Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer

Abstract

Tumor-infiltrating lymphocytes (TILs) in gastric cancer are closely related to clinical prognosis; however, little is known regarding the immune microenvironment in this disease. Thus, RNA-sequencing data from gastric cancer patients were downloaded from the Gene Expression Omnibus (GEO). The proportion of immune cells was determined based on a deconvolution algorithm (CIBERSORT), and gene expression profiles were analyzed in the context of clinical outcomes to construct an immune risk score. Data were analyzed using least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression, to identify prognostic markers of gastric cancer survival. The model included four immune cell types: neutrophils, plasma cells, activated CD4 + memory T cells, and T follicular helper cells. Patients were classified into two subgroups based on risk score, and a significant difference in overall survival (OS) was seen between the subgroups in both the training and testing cohorts, particularly in patients with tumor stages ≥T3. Multivariable analysis revealed that both T-stage and risk score were independent prognostic factors for gastric cancer survival [hazard ratio (HR) 1.505; 95% confidence interval (CI) 1.043-2.173, HR 1.686; 95% CI 1.367-2.080]. Risk scores and clinical factors were then integrated into a nomogram to build a model with both good discriminatory power and accuracy in predicting clinical outcomes. Further analysis using gene set enrichment analysis (GSEA) identified strong associations of immune risk with TGF-β and tumor metastasis-related pathways, which could inform research on the molecular mechanisms of gastric cancer. Collectively, the data presented here suggest that an immune risk model can make an important contribution to predictions prognosis in gastric cancer patients.

Prognostic and Immunological Value of GNB4 in Gastric Cancer by Analyzing TCGA Database

“…Many studies have reported the positive association of high TILs level with survival of multiple tumors, like breast cancer (BC) [ 33 ] or non-small-cell lung cancer (NSCLC) [ 34 ], which improves the curative effect of neoadjuvant chemotherapy in breast cancer [ 35 ]. In addition, TILs are known as predictive prognostic markers for gastric cancer [ 36 , 37 ]. However, some studies have shown that TILs exhibit no correlation with gastric cancer prognosis [ 38 ].…”

Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer

“…In subsequent work, we will collect information from GC patients who have undergone immunotherapy to further explore the influence of the TIIC score on therapeutic benefits. Many solid tumors are associated with immune cell infiltration in the tumor immune microenvironment, which affects therapy efficacy and overall survival to no small extent, yet the predictive role of individual cells on tumor prognosis is limited ( 38 , 39 ). It is hypothesized that the integration of multiple immune cells may improve the prediction of prognosis for GC patients.…”

LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

“…Memory B cells, plasma cells and NK activated cells all have a downward trend, although not all of them have significant statistical differences. In gastric cancer, 28 the activated CD4 + memory T cells and plasma cells, 29 contrary to resting CD4 + memory T cells, has been known as a protective factor. And for macrophages, 30 the 2 main polarization-based subtypes have more or less opposite functions in tumor: M1 macrophages are believed to exert anti-tumor effect by promoting the Th1 immune response; M2 macrophages favor the Th2 immune response, which facilitates tumor progression.…”