Predicting the Prognosis of Bladder Cancer Patients Through Integrated Multi-omics Exploration of Chemotherapy-Related Hypoxia Genes.

ABSTRACT

Bladder cancer is a prevalent malignancy with high mortality rates worldwide. Hypoxia is a critical factor in the development and progression of cancers. However, whether and how hypoxia-related genes (HRGs) could affect the development and the chemotherapy response of bladder cancer is still largely unexplored. This study comprehensively explored the complex molecular landscape associated with hypoxia in bladder cancer by analyzing 260 hypoxia genes based on transcriptomic and genomic data in 411 samples. Employing the 109 dysregulated hypoxia genes for consensus clustering, we delineated two distinct bladder cancer clusters characterized by disparate survival outcomes and distinct oncogenic roles. We defined a HPscore that was correlated with a variety of clinical features, including TNM stages and pathologic grades. Tumor immune landscape analysis identified three immune clusters and close interactions between hypoxia genes and the various immune cells. Utilizing a network-based method, we defined 129 HRGs exerting influence on apoptotic processes and critical signaling pathways in cancer. Further analysis of chemotherapy drug sensitivity identified potential drug-target HRGs. We developed a Risk Score model that was related to the overall survival of bladder cancer patients based on doxorubicin-target HRGs ACTG2, MYC, PDGFRB, DHRS2, and KLRD1. This study not only enhanced our understanding of bladder cancer at the molecular level but also provided promising avenues for the development of targeted therapies, representing a significant step toward the identification of effective treatments and addressing the urgent need for advancements in bladder cancer management.