• Sha Zhu, Jinge Zhao, Ling Nie, Wenlian Yin, Yaowen Zhang, Fengnian Zhao, Yuchao Ni, Xingming Zhang, Zhipeng Wang, Jindong Dai, Zhenhua Liu, Junru Chen, Yuhao Zeng, Zilin Wang, Guangxi Sun, Jiayu Liang, Xiaochen Zhao, Xudong Zhu, Ronggui Tao, Jiyu Yang, Ben He, Ni Chen, Pengfei Shen, and Hao Zeng.
• Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
• Bmc Med. 2022 Jul 22; 20 (1): 237.

BackgroundIntraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.MethodsThis study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.ResultsThe median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.ConclusionsM1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.© 2022. The Author(s).

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