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A miRNA signature predicts benefit from addition of hypoxia-modifying therapy to radiation treatment in invasive bladder cancer
Khan, Mairah T Irlam-Jones, Joely J Pereira, Ronnie R Lane, Brian Valentine, Helen R Aragaki, K. Dyrskjøt, L. McConkey, D. J. Hoskin, Peter J Choudhury, Ananya
Khan, Mairah T
Irlam-Jones, Joely J
Pereira, Ronnie R
Lane, Brian
Valentine, Helen R
Aragaki, K.
Dyrskjøt, L.
McConkey, D. J.
Hoskin, Peter J
Choudhury, Ananya
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Abstract
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
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Date
2021
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Khan MT, Irlam-Jones JJ, Pereira RR, Lane B, Valentine HR, Aragaki K, et al. A miRNA signature predicts benefit from addition of hypoxia-modifying therapy to radiation treatment in invasive bladder cancer. Br J Cancer. 2021 Apr 12