Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
J Transl Med. 2022 Jul 14;20(1):313. doi: 10.1186/s12967-022-03513-5.
Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately.
We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry.
Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort.
This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.
同源重组缺陷（HRD）与前列腺癌（PCa）患者的预后和治疗选择密切相关。然而，目前缺乏与 HRD 相关的定量指标来准确预测 PCa 的预后。
我们基于 HRD 评分筛选 HRD 相关基因，并构建 HRD 聚类系统，以探索聚类之间不同的临床病理、基因组和免疫基因组模式。通过多变量 Cox 回归分析建立并评估 HRDscore 风险特征。我们注意到，模型基因 SLC26A4 具有独特的预测 PCa 预后和 HRD 的潜力。进行了多组学分析以探讨其在 PCa 中的作用，并通过 qRT-PCR 和免疫组织化学验证了结果。
确定了 3 个 HRD 聚类，它们在患者预后、临床病理特征、生物学途径、免疫浸润特征和免疫调节剂调节方面存在显著差异。进一步分析表明，构建的 HRDscore 系统是 PCa 患者独立的预后因素，具有良好的稳定性。最后，我们确定了一个单基因 SLC26A4，它在三个独立队列中与预后显著相关。重要的是，SLC26A4 在我们的队列中分别在 RNA 和蛋白质水平上都能区分 PCa（mRNA 的 AUC 为 0.845；免疫组织化学评分的 AUC 为 0.769）和 HRD（mRNA 的 AUC 为 0.911；免疫组织化学评分的 AUC 为 0.689）。
本研究引入 HRDscore 来量化个体 PCa 患者的 HRD 模式。同时，SLC26A4 是一种新的生物标志物，可以合理地预测 PCa 的预后和 HRD。
