ESTRO 2025 - Abstract Book

S2118

Clinical - Urology

ESTRO 2025

4290

Mini-Oral Genomic landscape of hypoxia in bladder cancer Amen Shamim 1 , Conrado Guerrero Quiles 1 , Vanesa Biolatti 1 , Taha Lodhi 1 , Peter Hoskin 1,2 , Catharine ML West 1 , Ananya Choudhury 1,3 1 Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, Manchester, United Kingdom. 2 Mount Vernon, Cancer Centre, Northwood, United Kingdom. 3 Christie NHS Foundation, Trust, Manchester, United Kingdom Purpose/Objective: Hypoxia drives tumour progression in bladder cancer by activating hypoxia-responsive pathways and increasing genomic instability, creating a unique genomic landscape 1,2,3 . This study aimed to characterise hypoxia levels in bladder cancer and map the corresponding genomic landscape, with the goal of identifying potential targets that can aid in patient selection for hypoxia-modifying treatments to improve clinical outcomes. Material/Methods: Hypoxia scores were calculated for muscle-invasive bladder cancer (TCGA-BLCA) cohort (n=406) samples using available mRNA expression data. Patients were classified into “High” and “Low” using the median hypoxia -score of the cohort. To benchmark these findings, hypoxia scores for corresponding normal bladder tissues were also computed. A comparative analysis assessed the differential hypoxia levels between tumour and normal samples. The dataset was further enriched by incorporating published driver mutation data, enabling the summary of mutational features at the gene level and the identification of copy number variations (CNVs) for each sample. Associations between high hypoxia scores and specific driver mutations or CNVs were evaluated using logistic regression to identify potential relationships. Results: We identified a set of CNVs (103,181 total) across all patients within the TCGA-BLCA cohort. Logistic regression showed hypoxic tumours had increased genomic instability (Figure 1a), suggesting hypoxia induces specific genomic alterations. To better characterise these changes, we performed a genome-wide and chromosome-specific screening of CNVs (Figure 2b). Overall, we found that 70% of all identified CNVs alterations were found within the “High” hypoxia -scores groups, confirming our previous findings. Specifically, chromosomes 12, 14, 17 and 18 showed the highest levels of CNVs alterations. Interestingly, chromosomes 1, 4 and 6 showed a slight decrease in CNVs number, altogether suggesting hypoxia drives a complex regulation of the genome instability.

Figure 1: (a) Distribution of hypoxia scores in muscle-invasive bladder cancer patients. (b) Copy number variations (CNVs) across chromosomes, correlated with hypoxia levels in bladder cancer.