ArticleJournal of gastrointestinal cancer2025
Homologous Recombination Deficiency Is Associated with Shorter Survival in Colorectal Cancer Patients.
Article in Journal of gastrointestinal cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Construction and Validation of Multi-Omics Predictive Models for Colorectal Cancer Using Machine-Learning Approaches.Pharmacogenomics and personalized medicine · 2026Article
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8 authors.
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Abstract
backgroundColorectal cancer (CRC) patients benefit more from immune checkpoint inhibitor therapy, but they only account for around 15% of all patients. The remaining patients still lack effective therapeutic biomarkers to predict their prognosis.
methodsWe performed whole-exome sequencing (WES) to analyze 84 CRC specimens, classifying them into different groups based on their microsatellite status (MS), tumor mutation burden (TMB), homologous recombination deficiency (HRD) score, and clinicopathological features, which might be associated with clinical outcomes. Survival analysis and multivariable Cox regression modeling were employed to identify prognostic indicators. Comparative genomic profiling evaluated somatic mutations, copy number variations (CNVs), and pathway activation patterns across clinical subgroups.
resultsThe characteristics of the cohort (N = 84) revealed a median age of 52 years, with a male predominance (61.9%) and a majority of patients presenting with stage IV disease (77%). The HRD-high (HRD-H) subgroup accounted for 16.7%, while 19.0% of cases were microsatellite instability-high (MSI-H) and 22.6% were TMB-high (TMB-H). Multivariable analysis identified HRD-H as an independent predictor of overall survival (OS: HR = 0.19, 95% CI 0.12-0.94, p = 0.002). Comparative genomics demonstrated distinct mutation landscapes between HRD-H and HRD-low subgroups. In microsatellite-stable (MSS) patients, HRD-H status correlated with enriched SMAD4 mutations (p < 0.01) and differential activation of TGF-β/MYC signaling pathways compared to HRD-H-MSI counterparts.
conclusionHRD status serves as a novel independent prognostic biomarker in CRC. Our multi-parametric genomic framework delineates stratification-specific molecular signatures, advocating for HRD-integrated molecular diagnostics to optimize CRC management.
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