CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

作者：Yutao Wang, Kexin Yan, Jiaxing Lin, Yang Liu, Jianfeng Wang, Xuejie Li, Xinxin Li, Zhixiong Hua, Zhenhua Zheng, Jianxiu Shi, Siqing Sun, Jianbin Bi · 发表于：Frontiers in Oncology · 年份：2020 · DOI：10.3389/fonc.2020.553399 · 被引用次数：42 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Atherosclerosis and Cardiovascular Diseases

Purpose To identify immune-related co-expressed genes that promote CD8 + T cell infiltration in bladder cancer, and to explore the interactions among relevant genes in the tumor microenvironment. Method We obtained bladder cancer gene matrix and clinical information data from TCGA, GSE32894 and GSE48075. The “estimate” package was used to calculate tumor purity and immune score. The CIBERSORT algorithm was used to assess CD8 + T cell proportions. Weighted gene co-expression network analysis was used to identify the co-expression modules with CD8 + T cell proportions and bladder tumor purity. Subsequently, we performed correlation analysis among angiogenesis factors, angiogenesis inhibitors, immune inflammatory responses, and CD8 + T cell related genes in tumor microenvironment. Results A CD8 + T cell related co-expression network was identified. Eight co-expressed genes ( PSMB8 , PSMB9 , PSMB10 , PSME2 , TAP1 , IRF1 , FBOX6 , ETV7 ) were identified as CD8 + T cell-related genes that promoted infiltration of CD8 + T cells, and were enriched in the MHC class I tumor antigen presentation process. The proteins level encoded by these genes ( PSMB10 , PSMB9 , PSMB8 , TAP1 , IRF1 , and FBXO6 ) were lower in the high clinical grade patients, which suggested the clinical phenotype correlation both in mRNA and protein levels. These factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. PD-1 and PD-L1 positively correlated with th...