High expression of CXCL9 gene promotes immune invasion and improves the prognosis of patients with endometrial cancer

Abstract

Objective: CXCL9 plays a key role in immune cell chemotaxis and inhibition of tumor angiogenesis. The aim of this study was to investigate the prognostic value of CXCL9 in endometrial cancer (EC) and the impact on the immune microenvironment. Methods：RNA sequencing data for EC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, while clinicopathological information for EC patients was obtained from the TCGA database. Cox univariate and multivariate analyses were used, followed by the construction and validation of nomograms. CXCL9 expression and survival analysis, gene correlation and immune infiltration correlation analysis, and pathway enrichment analysis were performed using UALCAN, Kaplan-Meier, GeneMANIA, STRING, TIMER, cBioPortal, muTarget, CIBERSORT, TISIDB, GO, KEGG and GSEA tools. Results：CXCL9 was significantly upregulated in EC. Cox univariate and multivariate analysis showed that CXCL9 was an independent predictor of overall survival (OS), disease specific survival (DSS) and progression free interval (PFI) (P<0.05). However, increased CXCL9 expression predicted prolonged OS, DSS and PFI (P<0.05). In addition, CXCL9 was positively correlated with immune cell infiltration and correlated with marker genes of multiple immune pathways as well as marker genes of immune checkpoints. GSEA enrichment analysis suggests that high CXCL9 expression plays an important role in immune cell migration, activation and other functions. Conclusion: The results of this study suggest that high CXCL9 expression was a predictor of good prognosis in patients with EC and may be associated with the recruitment of immune cells to the tumor microenvironment in the tumor tissue to function as an anti-tumor immune response.