Li Tianhang, Jiang Ning, Bai Yuhao, Liu Tianyao, Zhao Zihan, Xu Xinyan, Zhang Yulin, Wei Fayun, Sun Rui, Liu Siyang, Li Jiazheng, Guo Hongqian, Yang Rong
Department of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.
Heliyon. 2023 Feb 13;9(3):e13661. doi: 10.1016/j.heliyon.2023.e13661. eCollection 2023 Mar.
To analyze the correlations between the expression and effect of DNA damage repair genes and the immune status and clinical outcomes of urothelial bladder cancer (BLCA) patients. In addition, we evaluate the efficacy and value of utilizing the DNA damage repair genes signature as a prognosis model for BLCA.
Two subtype groups (C1 and C2) were produced based on the varied expression of DNA damage repair genes. Significantly differentiated genes and predicted enriched gene pathways were obtained between the two subtypes. Seven key genes were obtained from the DNA damage repair-related genes and a 7-gene signature prognosis model was established based on the key genes. The efficacy and accuracy of this model in prognosis prediction was evaluated and verified in two independent databases. Also, the difference in biological functions, drug sensitivity, immune infiltration and affinity between the high-risk group and low-risk group was analyzed.
The DNA damage repair gene signature could significantly differentiate the BLCA into two molecular subgroups with varied genetic expression and enriched gene pathways. Seven key genes were screened out from the 232 candidate genes for prognosis prediction and a 7-gene signature prognosis model was established based on them. Two independent patient cohorts (TCGA cohort and GEO cohort) were utilized to validate the efficacy of the prognosis model, which demonstrated an effective capability to differentiate and predict the overall survival of BLCA patients. Also, the high-risk group and low-risk group derived from the 7-gene model exhibited significantly differences in drug sensitivity, immune infiltration status and biological pathways enrichment.
Our established 7-gene signature model based on the DNA damage repair genes could serve as a novel prognosis predictive tool for BLCA. The differentiation of BLCA patients based on the 7-gene signature model may be of great value for the appropriate selection of specific chemotherapy agents and immune-checkpoint blockade therapy administration.
分析DNA损伤修复基因的表达与作用与膀胱尿路上皮癌（BLCA）患者免疫状态及临床结局之间的相关性。此外，我们评估利用DNA损伤修复基因特征作为BLCA预后模型的疗效和价值。
根据DNA损伤修复基因的不同表达产生两个亚型组（C1和C2）。获得了两个亚型之间显著分化的基因和预测的富集基因途径。从DNA损伤修复相关基因中获得7个关键基因，并基于这些关键基因建立了一个7基因特征预后模型。在两个独立数据库中评估并验证该模型在预后预测中的疗效和准确性。同时，分析了高危组和低危组在生物学功能、药物敏感性、免疫浸润和亲和力方面的差异。
DNA损伤修复基因特征可将BLCA显著分为两个具有不同基因表达和富集基因途径的分子亚组。从232个候选基因中筛选出7个关键基因用于预后预测，并基于它们建立了一个7基因特征预后模型。利用两个独立的患者队列（TCGA队列和GEO队列）验证预后模型的疗效，该模型显示出有效区分和预测BLCA患者总生存期的能力。此外，由7基因模型衍生的高危组和低危组在药物敏感性、免疫浸润状态和生物途径富集方面表现出显著差异。
我们基于DNA损伤修复基因建立的7基因特征模型可作为BLCA一种新的预后预测工具。基于7基因特征模型对BLCA患者进行区分，可能对特定化疗药物的适当选择和免疫检查点阻断治疗的实施具有重要价值。
