A hypoxia transcriptomic signature to predict benefit from hypoxia-modifying treatment for muscle-invasive bladder cancer patients.

301Background: Hypoxia modification improves overall survival (OS) in muscle invasive bladder cancer (MIBC) patients treated with radical radiotherapy. There is evidence that hypoxic tumours benefit most from hypoxia modification. The study aimed to identify or derive a hypoxia gene signature that predicts benefit from hypoxia-modifying treatment in MIBC. Methods: Bladder cancer transcriptomic data were available from public datasets and generated for 152 tumour samples from the BCON phase III trial of radiotherapy (RT) alone or RT with carbogen and nicotinamide (CON) using Affymetrix Human 1.0 Exon ST arrays. Published hypoxia signatures were tested. A novel signature was then derived by identifying candidate hypoxia genes from the literature and evaluating their bladder cancer specificity in the publically available datasets. A gene co-expression network was built and hub genes identified to generate a signature. Results: None of the published hypoxia signatures were prognostic in public datasets or pre...