The role of TMEM119 in gastric adenocarcinoma and its specific effects on immunity

Abstract

Objective To investigate the prognostic significance and immunological implication of transmembrane protein 119 (TMEM119) in stomach adenocarcinoma (STAD). Methods This study included STAD-associated data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, TMEM119 expression levels were analysed by immunohistochemistry in tissue samples from patients with STAD (with microsatellite instability or microsatellite stability). Gene Set Enrichment Analysis (GSEA) was conducted to explore signalling pathways related to TMEM119 in STAD. Additionally, CIBERSORT and ESTIMATE algorithms were applied to examine the relationship between TMEM119 expression and tumour-infiltrating immune cells, as well as the tumour microenvironment. Results Surgical specimens from 100 patients with STAD (50 each with microsatellite stability or microsatellite instability); TCGA RNA-sequence and clinical data from 375 STAD tumour tissues and 32 paracancerous tissues; and two GEO datasets (GSE27342, comprising 80 paracancerous tissues and 80 tumour tissues; and GSE84437, comprising 433 tumour samples) were analysed. TMEM119 was found to be elevated in STAD, and associated with poor prognosis. Clinical gastric cancer tissues exhibited increased TMEM119 expression. TMEM119 was enriched in immune-related functions and pathways. TMEM119 correlated with immune checkpoint genes, tumour mutational burden, and microsatellite instability. TMEM119 was positively correlated with tumour-infiltrating immune cells, tumour microenvironment, mannose receptor C-type I (CD206), and programmed cell death-ligand 1 (PD-L1), while inversely related to nitric oxide synthase 2. Conclusions TMEM119 may be a potential immune-related biomarker for STAD prognosis and therapeutic targeting.