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Discovering a qualitative transcriptional signature of homologous recombination defectiveness for prostate cancer
iScience ( IF 5.8 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.isci.2021.103135
Yawei Li 1 , Zhangxiang Zhao 1 , Liqiang Ai 1 , Yuquan Wang 1 , Kaidong Liu 1 , Bo Chen 1 , Tingting Chen 1 , Shuping Zhuang 1 , Huanhuan Xu 1 , Min Zou 1 , Yunyan Gu 1 , Xia Li 2
Affiliation  

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.



中文翻译:

发现前列腺癌同源重组缺陷的定性转录特征

前列腺癌中同源重组缺陷 (HRD) 生物标志物的发现对于将从聚 ADP-核糖聚合酶抑制剂 (PARPi) 中受益的患者非常重要。在这里,我们通过基于相对表达排序 (REO) 的发现程序开发了前列腺癌的转录同源重组缺陷 (HRDness) 特征,包括 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 特征中显示出比通过其他方法(如 HRDetect)获得的亚型更高的显着性水平。在三个独立的数据集中,HRDness 亚型还显示出比非 HRDness 更具攻击性的特征和更高的基因组学分数。HRDness 前列腺癌细胞对PARPi 比非HRDness 更敏感。而且,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,新提出的定性特征可以在个性化水平上有力地确定前列腺癌的 HRD 状态,尤其是 PARPi 治疗策略的辅助工具。

更新日期:2021-09-28
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