A miRNA signature predicts benefit from addition of hypoxia-modifying therapy to radiation treatment in invasive bladder cancer

Background miRNAs are promising biomarkers in oncology as their small size makes them less susceptible to degradation than mRNA in FFPE tissue. We aimed to derive a hypoxia-associated miRNA signature for bladder cancer. Methods Taqman miRNA array cards identified miRNA seed genes induced under hypoxia in bladder cancer cell lines. A signature was derived using feature selection methods in a TCGA BLCA training data set. miRNA expression data were generated for 190 tumours from the BCON Phase 3 trial and used for independent validation. Results A 14-miRNA hypoxia signature was derived, which was prognostic for poorer overall survival in the TCGA BLCA cohort ( n = 403, p = 0.001). Univariable analysis showed that the miRNA signature predicted an overall survival benefit from having carbogen–nicotinamide with radiotherapy (HR = 0.30, 95% CI 0.094–0.95, p = 0.030) and performed similarly to a 24-gene mRNA signature (HR = 0.47, 95% CI 0.24–0.92, p = 0.025). Combining the signatures improved performance (HR = 0.26, 95% CI 0.08–0.82, p = 0.014) with borderline significance for an interaction test ( p = 0.065). The interaction test was significant for local relapse-free survival LRFS ( p = 0.033). Conclusion A 14-miRNA hypoxia signature can be used with an mRNA hypoxia signature to identify bladder cancer patients benefitting most from having carbogen and nicotinamide with radiotherapy.