Definition of a Novel Immunogenic Cell Death-Relevant Gene Signature Associated with Immune Landscape in Gastric Cancer.

Abstract

Immunogenic cell death (ICD) induces anti-tumor immunity and aids in dismantling the immunosuppressive immune microenvironment (TME), which belongs to a type of regulated cell death. The differentiation of gastric cancer (GC) subtypes and the discovery of prognostic biomarkers are crucial for its treatment because GC is a disease that is both highly heterogeneous and aggressive. However, although the induction of ICD in tumor cells is associated with afavorableprognosis, the exact mechanism of its role in GC remains unclear. Transcriptome profiling data and clinical data of GC patients were retrieved from The Cancer Genome Atlas (TCGA) database. Herein, patients were classified with the consensus clustering algorithm, and the associated biological functions and immune microenvironment infiltration were explored based on the expression of ICD-associated genes. A risk score signature consisting of 11 ICD-related genes was established via the least absolute shrinkage and selection operator regression (LASSO) method. We have retrieved similar studies in recent years and compared them with our study using the time-dependent receiver operating characteristic (ROC) curves. Gene set variation analysis (GSVA) and single sample gene set enrichment analysis (ssGSEA) were performed to explore the association between the signature and tumor microenvironment (TME). Two distinct subtypes associated with ICD in GC were identified, each with a different prognosis. The ICD-high expression subtype was associated with higher immune cell infiltration and a better prognosis. The ICD-related gene signature containing 11 genes (CGB5, Z84468.1, APOA5, EPHA8, CLEC18C, TLR7, MUC7, MUC15, CTLA4, CALB2, and UGT2B28), could independently and accurately predict the prognosis of GC. In this study, an ICD-based classification was conducted to assist in the diagnosis and personalized therapy for GC. The ICD-related genes risk score model was established to predict prognosis.