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.
Highlights
Bladder cancer is the most frequent cancer in the urinary system, which is estimated to have 81,400 new diagnosed cases and 17,980 deaths in the United States in 2020 (Siegel et al, 2020)
The hypoxia-related gene set downloaded from the Gene Set Enrichment Analysis (GSEA) database contained 200 genes up-regulated in response to a low oxygen level
A total of 48 genes were selected by univariate Cox regression analysis as they were significantly associated with bladder cancer patients’ disease-specific survival (DSS)
Summary
Bladder cancer is the most frequent cancer in the urinary system, which is estimated to have 81,400 new diagnosed cases and 17,980 deaths in the United States in 2020 (Siegel et al, 2020). Previous studies have found hypoxia microenvironments played an important role in progression, metastasis, and angiogenesis in bladder cancer (Reiher et al, 2001; Luo et al, 2019; Su et al, 2019). Immune feature is another vital feature and immunotherapy has Hypoxia-Related Signature for Bladder Cancer shown great potential in treatment for bladder cancer (Kamat et al, 2017; Koshkin and Grivas, 2018; Marshall and Djamgoz, 2018). The hypoxia feature may be utilized as a biomarker to predict the immune microenvironment (IME) and the efficacy of immunotherapy
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