BMC Medicine (Jul 2022)

Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P)

  • 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,
  • Hao Zeng

DOI
https://doi.org/10.1186/s12916-022-02430-0
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

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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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