A miRNA signature predicts benefit from addition of hypoxia-modifying therapy to radiation treatment in invasive bladder cancer
AuthorsKhan, Mairah T.
Irlam-Jones, Joely J.
Pereira, Ronnie Rodrigues
Valentine, Helen R.
McConkey, David J.
Hoskin, Peter J.
West, Catharine M. L.; orcid: 0000-0002-0839-3449; email: Catharine.West@manchester.ac.uk
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AbstractAbstract: 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.
CitationBritish Journal of Cancer, volume 125, issue 1, page 85-93
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-09-03, rev-recd 2021-02-11, accepted 2021-02-19, registration 2021-02-19, pub-electronic 2021-04-12, online 2021-04-12, pub-print 2021-07-06
Publication status: Published
Funder: U.S. Department of Defense (United States Department of Defense); doi: https://doi.org/10.13039/100000005; Grant(s): W81XWH-17-1-0543