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Identification of a Hypoxia-Related Signature for Predicting Prognosis and the Immune Microenvironment in Bladder Cancer

Minxiao Jiang, Liangliang Ren, Yuanlei Chen, Huan Wang, Haiyang Wu, Sheng Cheng, Gonghui Li, Shicheng Yu
Frontiers in Molecular Biosciences , Volume 8; doi:10.3389/fmolb.2021.613359

Abstract: Accumulating evidence indicates that hypoxia is highly associated with bladder cancer genesis, progression, and immune microenvironment. Nevertheless, few studies have identified the role of hypoxia-related genes as a prognostic signature in bladder cancer. This study aimed to establish a hypoxia-related signature with high accuracy for prognosis and immune microenvironment prediction in bladder cancer. We obtained expression profiles and clinical information from Gene Expression Omnibus and The Cancer Genome Atlas. Then the univariate Cox regression, random survival forest algorithm, and multivariate Cox regression analysis were conducted to identify the core genes and four hypoxia-related genes (ANXA2, GALK1, COL5A1, and HS3ST1) were selected to construct the signature. Kaplan-Meier survival analysis demonstrated that patients with a low-risk score had a higher disease-specific survival rate (p < 0.0001). The areas under the curve of the signature were 0.829 at 1 year, 0.869 at 3 years, and 0.848 at 5 years, respectively. Additionally, we found this hypoxia-related signature was highly correlated with tumor immune microenvironment and had the potential to predict the efficacy of immunotherapy. In summary, our study developed a hypoxia-related signature, which had high accuracy for prognosis prediction and the potential to guide the immunotherapy for bladder cancer patients.
Keywords: hypoxia / Immunotherapy / prediction / immune microenvironment / Bladder cancer / disease-specific survival

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