A Robust Hypoxia Risk Score Predicts the Clinical Outcomes and Tumor Microenvironment Immune Characters in Bladder...

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Bladder cancer (BLCA) is a common malignancy with a poor prognosis.
• There is a critical need for tools to predict BLCA prognosis and treatment response.

Purpose of the Study:

• To develop and validate a hypoxia risk score for predicting clinical outcomes and tumor microenvironment (TME) characteristics in BLCA.
• To assess the score's potential in guiding precision medicine for BLCA.

Main Methods:

• Collected hypoxia-related genes and utilized The Cancer Genome Atlas (TCGA-BLCA) cohort.
• Employed Cox regression with LASSO algorithm to develop a hypoxia risk score.
• Validated the score using internal, external, and hospital-based cohorts, correlating it with clinical outcomes, TME, and treatment efficacy.

Main Results:

• The hypoxia risk score is an independent prognostic factor for BLCA.
• A high-risk score correlates with an inflamed TME, increased immune cell infiltration (CD8+ T cells, Dendritic cells, NK cells), and higher expression of immune checkpoints (PD-L1, PD-1, CTLA-4, LAG-3).
• The score predicts sensitivity to immunotherapy, chemotherapy (Cisplatin, Docetaxel, Paclitaxel, etc.), and radiotherapy, while low-risk scores associate with immunosuppressive pathways.

Conclusions:

• A novel hypoxia risk score effectively predicts BLCA clinical outcomes and TME immune characteristics.
• This score shows promise as a tool to aid in the development of precision medicine strategies for bladder cancer.