伴有或不伴有前列腺内导管癌的侵袭性前列腺腺癌的同源重组缺陷（HRD）评分。

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

机构信息

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

BMC Med. 2022 Jul 22;20(1):237. doi: 10.1186/s12916-022-02430-0.

DOI:10.1186/s12916-022-02430-0

PMID:35864546

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9306093/

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.

摘要

背景

前列腺导管内癌（IDC-P）是一种预后不良的前列腺癌亚型。先前的研究表明，IDC-P 可能具有潜在不稳定的基因组。同源重组缺陷（HRD）评分是一种描述基因组不稳定性状态的结果导向方法。本研究旨在探讨 HRD 评分与 IDC-P 及其他临床病理因素的相关性，以及 HRD 评分在侵袭性前列腺癌队列中的预后意义。

方法

本研究纳入了 123 例前列腺癌患者，包括高危局限性（M0）和新发转移性（M1）疾病。HRD 评分是基于分布在人类基因组中的 10000 多个单核苷酸多态性计算得出的。我们使用秩和检验、卡方检验、Kaplan-Meier 曲线和 Cox 比例风险方法，探讨了 HRD 评分与临床病理特征、基因组改变和患者预后之间的关系。

结果

该队列的中位 HRD 评分为 21.0，其中 65 例（52.8%）患者的 HRD 评分≥21.0。IDC-P 肿瘤的 HRD 评分高于腺癌（P=0.002）；其他与高 HRD 评分相关的因素包括 M1（P=0.008）和高 ISUP 分级（4-5）（P=0.001）。在总队列中，MYC 突变与高 HRD 评分相关（P<0.001）。TP53 突变（P=0.010）和 HRR 通路突变（P=0.028）分别与 IDC-P 阳性和非 IDC-P 患者的高 HRD 评分相关，但反之则不相关。HRD 评分高于 21.0 提示总队列的生存明显较差。