Li Yawei, Zhao Zhangxiang, Ai Liqiang, Wang Yuquan, Liu Kaidong, Chen Bo, Chen Tingting, Zhuang Shuping, Xu Huanhuan, Zou Min, Gu Yunyan, Li Xia
Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Department of Bioinformatics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
iScience. 2021 Sep 17;24(10):103135. doi: 10.1016/j.isci.2021.103135. eCollection 2021 Oct 22.
The discovery of homologous recombination deficiency (HRD) biomarkers in prostate cancer is important for patients who will benefit from poly ADP-ribose polymerase inhibitor (PARPi). Here, we developed a transcriptional homologous recombination defectiveness (HRDness) signature, comprising 16 gene pairs (16-GPS), for prostate cancer by a relative expression ordering (REO)-based discovery procedure. Subsequently, two newly subtypes classified by 16-GPS showed a higher significance level in various clinicopathological and HRD features than subtypes obtained by other methods, such as HRDetect. HRDness subtype also displayed more aggressive features and higher genomics scores than non-HRDness in three independent datasets. HRDness prostate cancer cells were more sensitive to PARPi than non-HRDness. Moreover, the HRDness samples showed distinct multi-omics characteristics related to homologous recombination repair function loss. Overall, the newly proposed qualitative signature can robustly determine the HRD status for prostate cancer at the personalized level, and especially be an auxiliary tool for PARPi treatment strategy.
在前列腺癌中发现同源重组缺陷（HRD）生物标志物，对将从聚ADP核糖聚合酶抑制剂（PARPi）中获益的患者来说至关重要。在此，我们通过基于相对表达排序（REO）的发现程序，为前列腺癌开发了一种转录同源重组缺陷（HRDness）特征，该特征包含16个基因对（16-GPS）。随后，由16-GPS分类的两个新亚型在各种临床病理和HRD特征方面，比通过其他方法（如HRDetect）获得的亚型显示出更高的显著性水平。在三个独立数据集中，HRDness亚型也比非HRDness亚型表现出更具侵袭性的特征和更高的基因组学评分。HRDness前列腺癌细胞对PARPi比非HRDness更敏感。此外，HRDness样本显示出与同源重组修复功能丧失相关的独特多组学特征。总体而言，新提出的定性特征能够在个性化水平上有力地确定前列腺癌的HRD状态，尤其可作为PARPi治疗策略的辅助工具。
