Work

Prognostic value and immune landscape implications of using a novel homologous recombination repair pathway signature in prostate cancer: A retrospective cohort study

Year: 2026

Type: article

Abstract: Objective Although the homologous recombination repair (HRR) pathway plays a critical role in the treatment of prostate cancer, its prognostic value remains incompletely understood. This study aimed to identify HRR pathway–related biomarkers with clinical utility for prognosis prediction and treatment guidance. Methods We analyzed genomic data from The Cancer Genome Atlas and Chinese patients with prostate cancer in a retrospective cohort study using a comprehensive multiomics approach to characterize a novel HRR-related prognostic signature and its immune implications. Results In the Chinese cohort, 25.6% of the patients exhibited homologous recombination deficiency scores >42, whereas 27.3% carried ≥1 HRR gene mutation. We established a prognostic HRR signature (homologous recombination deficiency score >32, HRR gene mutations, and Signature 3) associated with poor outcomes. Compared with The Cancer Genome Atlas data, the Chinese cohort demonstrated a higher prevalence of HRR signature. Patients with HRR signatures demonstrated significantly increased genomic instability markers, including segment number, alteration burden, aneuploidy score, and intratumor heterogeneity. The HRR signature was associated with higher neoantigen load but reduced T cell receptor (TCR) evenness. Immunologically, HRR-positive tumors were associated with computationally inferred immune profiles suggestive of reduced immune activity, characterized by depletion of T-helper 17 cell; downregulation of TLR4 / PDCD1LG2 expression; and upregulation of ARG1 , IFNG , KIR2DL3 , and CXCL9 . However, these findings are descriptive and require experimental validation. Conclusion Our findings identify a clinically relevant HRR signature that warrants investigation as a potential predictive biomarker for prostate cancer prognosis and treatment response. This biomarker provides new insights for personalized therapy and may help optimize patient outcomes.

Source: Journal of International Medical Research

DOI: 10.1177/03000605261487253