Role of CXCR4 as a Prognostic Biomarker Associated With the Tumor Immune Microenvironment in Gastric Cancer

Abstract

Background: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, accounting for high rates of morbidity and mortality in the population. The tumor microenvironment (TME), which plays a crucial role in GC progression, may serve as an optimal prognostic predictor of GC. In this study, we identified CXC motif chemokine receptor 4 (CXCR4) as a TME-related gene among thousands of differentially expressed genes (DEGs). We showed that CXCR4 can be used to predict the effect of immunotherapy in patients with GC. Methods: GC samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for the presence of stroma (stromal score), the infiltration of immune cells (immune score) in tumor tissues, and the tumor purity (estimate score) using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm. DEGs were sorted based on differences in the values of the three scores. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological processes and pathways enriched in these DEGs. The correlations of scores with clinicopathological features and overall survival (OS) of patients with GC were assessed by the Kaplan–Meier survival and Cox regression analyses. Through subsequent protein–protein interaction (PPI) network and univariate Cox regression analyses, CXCR4 was identified as a TME-related gene. Gene Set Enrichment Analysis (GSEA) was performed to assess the role of CXCR4 in the TME of GC. The CIBERSORT algorithm was used to further explore the correlation between tumor-infiltrating immune cells (TIICs) and CXCR4. Finally, the TISIDB database was used to predict the efficacy of immunotherapy in patients with GC. Results: We extracted 1231 TME-related DEGs and by an overlapping screening of PPI network and univariate Cox regression, CXCR4 was identified as a biomarker of TME, which deeply engaged in immune-related biological processes of gastric cancer and have close association with several immunocompetent cells. Conclusion: CXCR4 may be a useful biomarker of prognosis and an indicator of the TME in GC.