CXCL12, a potential modulator of tumor immune microenvironment (TIME) of bladder cancer: From a comprehensive analysis of TCGA database.

Abstract

Tumor immune microenvironment (TIME) plays a significant role in the initiation and progression of bladder urothelial carcinoma (BLCA). However, there are only a few researches regarding the association between immune-related genes and tumor-infiltrating immune cells (TICs) in TIME of BLCA. We calculated the proportion of immune/stromal component and TICs of 414 BLCA samples and 19 normal samples downloaded from TCGA database with the help of ESTIMATE and CIBERSORT algorithms. Differentially expressed genes (DEGs) were obtained from the comparison between Stromal and Immune Score and further analyzed by GO and KEGG enrichment analysis, as well as PPI network and COX regression analysis. CXCL12 was overlapping among the above analyses. Single gene analysis of CXCL12 was carried out through difference analysis, paired analysis and GSEA. The association between CXCL12 and TICs was assessed by difference analysis and correlation analysis. Immune and stromal component in TIME of BLCA were associated with patients' clinicopathological characteristics. 284 DEGs were primarily enriched in immune-associated activities, among which CXCL12 was the most significant gene sharing the leading nodes in PPI network and being closely related with patients' survival. Single gene analysis and immunohistochemistry revealed that CXCL12 was down-regulated in BLCA samples and significantly related with the clinicopathological characteristics of patients. Further analysis suggested that CXCL12 was involved in the immune-associated activities probably through its close cross-talk with TICs. CXCL12 down-regulation could be a potential biomarker to predict the unbalanced immune status of TIME of BLCA, which might provide an extra insight for the immunotherapy of BLCA.