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Zhu, Sha; Zhao, Jinge; Nie, Ling; Yin, Wenlian; Zhang, Yaowen; Zhao, Fengnian; Ni, Yuchao; Zhang, Xingming; Wang, Zhipeng; Dai, Jindong; Liu, Zhenhua; Chen, Junru; Zeng, Yuhao; Wang, Zilin; Sun, Guangxi; Liang, Jiayu; Zhao, Xiaochen; Zhu, Xudong; Tao, Ronggui; Yang, Jiyu; He, Ben; Chen, Ni; Shen, Pengfei; Zeng, Hao
BMC medicine, 07/2022, Volume: 20, Issue: 1Journal Article
Abstract Background Intraductal 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. Methods This 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. Results The 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. Conclusions M1, 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.
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