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

Autor: Khan MT; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., Irlam-Jones JJ; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., Pereira RR; Translational Oncogenomics, Cancer Research UK Manchester Institute, Oglesby Cancer Research Building, University of Manchester, Manchester, UK., Lane B; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., Valentine HR; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., Aragaki K; Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA., Dyrskjøt L; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., McConkey DJ; Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA., Hoskin PJ; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., Choudhury A; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK., West CML; Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK. Catharine.West@manchester.ac.uk.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2021 Jul; Vol. 125 (1), pp. 85-93. Date of Electronic Publication: 2021 Apr 12.
DOI: 10.1038/s41416-021-01326-9
Abstrakt: 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.
Databáze: MEDLINE
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