Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis

Abstract

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the composition of 22 tumor-infiltrating lymphocytes (TILs) in TCGA Stomach Adenocarcinoma (STAD) using deconvolution-based method by analyzing the publicly available bulk tumor RNA-seq data. The patients were classified into high-TIL and low-TIL subtypes based on their immune cell profiles and prognosis outputs. The differentially expressed genes (DEGs) between the two subtypes were identified, and GO/KEGG analysis showed that broad immune genes, such as PD-L1 and PD-1, were highly expressed in the high-TIL subtype. A comprehensive protein–protein interaction (PPI) network centered on DEGs was built, and 16 hub genes of the network were further identified. Based on the hub genes, an elastic model with 11 gene signatures (NKG7, GZMB, IL2RB, CCL5, CD8A, IDO1, MYH1, GNLY, CXCL11, GBP5 and PRF1) was developed to predict the high-TIL subtype. In summary, our findings showed that the compositions of TILs within the tumor immune microenvironment of stomach cancer patients are highly heterogeneous, and the profiles of TILs have the potential to be predictive markers of patients’ responses and overall survival outcomes.