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Hypoxia-Related Gene Signature: An Independent Clinical Predictor in Bladder Cancer?

By: Vanessa A. Carter, BS
Posted: Monday, June 28, 2021

Ye et al, of Shanghai Tenth People’s Hospital, Tongji University School of Medicine, China, and colleagues examined the role of a hypoxia-related gene signature in the prognostic and immune microenvironment in bladder cancer. Published in Cancer Cell International, their results identified the 7 hypoxia-related gene signature as a potential independent clinical predictor. They suggested that immunotherapy may prove ineffective in these patients due to their elevated mRNA expression levels of immunosuppressive genes.

RNA-sequencing data and clinical information on patients with bladder cancer were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Additionally, 45 paired cancer and paracancerous tissue samples were collected from patients with bladder cancer who underwent radical cystectomy to validate 7 hypoxia-related gene expression levels.

Compared with those with a low-risk score, samples with high-risk scores from both The Cancer Genome Atlas and the Gene Expression Omnibus databases demonstrated a significant association with poor overall survival outcomes (P < .001 and P = .024, respectively). A multivariate Cox analysis uncovered an independent correlation between risk score and overall survival. The AUC of the signature for predicting 1-, 3-, and 5-year overall survival of The Cancer Genome Atlas was 0.661, 0.676, and 0.710, respectively, and for the Gene Expression Omnibus, 0.600, 0.594, and 0.636.

When stratified by gender, age, and stage, patients at high risk still demonstrated significantly shorter overall survival than those at low risk, suggesting that the hypoxia-related signature may play a role. Of note, patients at low hypoxia risk had higher levels of follicular helper T cells, plasma cells, and CD8 T cells. In contrast, the high-risk group had a larger proportion of CD4 memory resting T cells, mast resting cells, and neutrophils.

Disclosure: The study authors reported no conflicts of interest.



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