Identification and validation of a hypoxia-related prognostic and immune microenvironment signature in bladder cancer
Xianchao Sun, Zhen Zhou, Ying Zhang, Jinyou Wang, Xiaofeng Zhao, Liang Jin, Ting‐Shuai Zhai, Xiang Liu, Jiaxin Zhang, Wangli Mei, Bihui Zhang, Ming Luo, Xudong Yao, Lin Ye
Abstract
BACKGROUND: Bladder cancer is the leading causes of cancer-associated mortality and seriously affects population health. Hypoxia plays a key role in tumor development and immune escape, which contributes to malignant behaviors. METHODS: In this study, we analyzed the RNA-seq and clinical information of bladder cancer patients from The Cancer Genome Atlas (TCGA) database. To investigate the hypoxia-related prognostic and immune microenvironment in bladder cancer, we constructed a hypoxia-related risk model for overall survival (OS). The RNA-seq and clinical data of bladder cancer patients from the Gene Expression Omnibus (GEO) database were used as validation sets. RESULTS: The hypoxia-related risk signature was significantly correlated with clinical outcomes and could independently predict OS outcomes. Furthermore, the hypoxia-related risk signature could effectively reflected the levels of immune cell type fractions and the expression of critical immune checkpoint genes were higher in the high-risk group compared to the low-risk group. We also validated the expression levels of the prognostic genes in bladder cancer and paracancerous tissue samples through qRT-PCR analysis. CONCLUSION: We established a 7 hypoxia-related gene (HRG) signature that can be used as an independent clinical predictor and provided a potential mechanism in bladder cancer immunotherapy.