Abstract
BackgroundBladder 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.MethodsIn 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.ResultsThe 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.ConclusionWe 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.
Highlights
Bladder cancer is the leading causes of cancer-associated mortality and seriously affects population health
Immune checkpoint molecules are significantly associated with regulation of the tumor microenvironment
We developed a hypoxia-related risk signature as a prognostic symbol to reflect the immune landscape in bladder cancer
Summary
Bladder cancer is the leading causes of cancer-associated mortality and seriously affects population health. Invasion and regulates immune responses [2, 3]. Sun et al Cancer Cell Int (2021) 21:251 studies have reported the mechanisms between tumor hypoxia and immune escape, indicating that hypoxia can be used to predict immunotherapeutic outcomes [10,11,12]. Immune checkpoint molecules are significantly associated with regulation of the tumor microenvironment. Immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been approved for immunotherapeutic management of various cancers. Under hypoxia in the tumor environment, cancer cells can adapt to support cellular survival and proliferation. Oxygen-deprived conditions inhibit activation of tumor-infiltrating lymphocytes, leading to an immunosuppressive environment and tumor immune escape. Tumor hypoxia is a potential therapeutic target in immunotherapy
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