期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms222111771
关键词
prostate cancer (PC); DNA damage repair (DDR); DDR-based transcriptomic biomarker; prognostic marker; cancer survival
资金
- Ministry of Science and Technology, Taiwan, R.O.C. [MOST 108-2314-B-037-079-MY3, MOST 109-2622-E-039-004-CC2, MOST 109-2628-E-039-001-MY3, MOST 109-2327-B-039-002, MOST109-2314-B-037-106-MY3, MOST 109-2320-B-037-007-MY3]
- Kaohsiung Medical University Chung-Ho Memorial Hospital [KMUH105-5M55]
- China Medical University Hospital [DMR-109-223, DMR-110-072, DMR-110-244]
- China Medical University, Taiwan, R.O.C. [CMU107-S-24, CMU108-Z-02, CMU108-S-22, CMU109-MF-61, CMU110-MF-64]
The importance of DDR and its application in PC has been acknowledged, with a four-gene panel identified as significantly associated with patient survival and progression. Higher expression of these genes is linked to worse outcomes, and the panel shows correlation with aggressiveness in PC.
In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes DNTT, EXO1, NEIL3, and EME2 genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据