Taipei City Hospital Renai Branch, Taipei 10629, Taiwan.
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2021 Oct 29;22(21):11771. doi: 10.3390/ijms222111771.
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 , , , and 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.
在最近十年中，DNA 损伤修复 (DDR) 的重要性及其在前列腺癌 (PC) 中的临床应用已得到充分认识。例如，奥拉帕利 (olaparib) 于 2020 年 5 月刚刚获批，用于治疗同源重组修复基因突变的转移性去势抵抗性 PC；然而，并非所有患者都能从奥拉帕利治疗中获益，治疗反应取决于患者的特定突变。这凸显了进一步了解详细的 DDR 生物学并开发基于 DDR 的生物标志物的必要性。在这项研究中，我们从 TCGA-PRAD 数据库中建立了一个与 PC 患者的总生存期 (OS) 和无进展生存期 (PFS) 显著相关的四个基因表达谱。该基因包括 、 、 、 基因。四个鉴定基因表达水平较高的患者 OS 和 PFS 明显较差。在调整年龄、PSA、TNM 分期和 Gleason 评分的多变量 Cox 回归模型中，也存在这种意义。此外，基于已知的 PAM50 和 PCS 亚分型分类器，四个基因表达谱与侵袭性高度相关。使用公开可用的数据库，我们成功验证了该四个基因表达谱具有作为基于 DDR 生物学的 PC 特定的预后和预测生物标志物的潜力。
