ArticleBiotech (Basel (Switzerland))2026
Hypoxia and DNA-Repair Radiosensitivity Signatures Are Associated with Radiotherapy-Modified Survival in TCGA Breast Cancer, with External Prognostic Validation of the Hypoxia Score in METABRIC.
Article in Biotech (Basel (Switzerland)), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Radiotherapy (RT) is one of the main treatments for breast cancer, but response varies between patients. Tumour hypoxia and intrinsic radiosensitivity are major determinants of response to RT. Using TCGA-BRCA, a 563-gene hypoxia meta-signature was built by combining curated hypoxia gene sets from MSigDB with published hypoxia metagenes (Buffa, Winter, Elvidge, Fardin, and related sets). After Cox screening and penalised regression, a simple three-gene hypoxia score (CP, GPC3, STC1) was derived. In parallel, based on DSB-repair factors highlighted by Mladenov et al. as key regulators of intrinsic radiosensitivity, a four-gene radiosensitivity (RS) signature (ATR, RPA2, BLM, MRE11A) was trained using only RT-treated patients. In TCGA, both signatures were prognostic and showed significant interaction with RT status in Cox models. The hypoxia score was strongly associated with worse outcomes in RT-untreated patients, but this effect was much weaker in RT-treated patients (Hypoxia × RT HR = 0.009,
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