Screening Potential Prognostic Factors for gastric carcinoma and Indicators for Tumor Microenvironment Remodeling in Female and Male patients Based on TCGA Data Mining

Abstract

Background: The tumour microenvironment (TME) is closely involved in the genesis and development of gastric carcinoma (GC). However, few studies have investigated the impact of sex on the dynamic modulation of immune and stromal components in the TME. Methods: In this review, we employed the CIBERSORT and ESTIMATE algorithms to analyse the ratio of tumour-infiltrating immune cells (TICs) and the number of immune and stromal components in 130 female and 218 male GC cases from The Cancer Genome Atlas (TCGA) database. COX regression analysis and a protein-protein interaction (PPI) network were conducted to analyse the differentially expressed genes (DEGs). Results: The results showed that the Fc fragment of IgG receptor IIa (FCGR2A) in females and GDNF family receptor alpha 1 (GFRA1) in males were predictive factors by intersection analysis of univariate COX and PPI. Moreover, FCGR2A was negatively correlated with the survival of female patients, while GFRA1 was positively related to the survival of male patients. Gene set enrichment analysis (GSEA) demonstrated that genes in the FCGR2A high expression group were primarily enriched in the antigen processing and presentation pathway, while genes in the GFRA1 low expression group were primarily enriched in the cell cycle and DNA replication pathway. Furthermore, CIBERSORT analysis of the proportion of TICs demonstrated that M2 macrophages were positively correlated with FCGR2A expression. B cells, T cells, monocytes and macrophages were positively related to GFRA1 expression. Conclusions The levels of FCGR2A and GFRA1 might be utilized to outline the prognosis of female and male GC patients, respectively. The results of this study demonstrate the impact of sex on tumour progression and may facilitate the development of therapeutics for GC patients.