Shao Yanxiang, Hu Xu, Yang Zhen, Lia Thongher, Yang Weixiao, Wu Kan, Ren Shangqing, Xiong Sanchao, Dou Weichao, Feng Shuyang, Wang Yaohui, Liu Yang, Wu Kang, Li Xiang
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People's Republic of China.
Department of Urology, Chengdu Second People's Hospital, Chengdu, People's Republic of China.
Cancer Cell Int. 2021 Jan 6;21(1):23. doi: 10.1186/s12935-020-01731-9.
To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer.
The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified.
A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden.
BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.
探讨非肌层浸润性膀胱癌复发的遗传预后因素。
患者接受经尿道膀胱肿瘤切除术，并接受卡介苗（BCG）或表柔比星治疗。进行二代测序，记录基因、信号通路改变及肿瘤突变负荷。评估这些临床病理和基因变异之间的关联，并确定预后因素。
本研究共纳入58例患者，46例接受BCG治疗。FGFR3是最常发生改变的基因（48%），在中危患者中更常见。单因素Cox分析显示，10个基因与BCG治疗失败显著相关，而NEB、FGFR1和SDHC是独立的复发预测因子。此外，表观遗传相关基因通路突变与复发呈负相关（风险比：0.198，P = 0.023）。DNA损伤反应和修复基因改变与肿瘤负荷呈正相关，其中TP53改变最为常见，且与高肿瘤负荷显著相关。
在该人群中，与表柔比星相比，BCG灌注显著降低了复发率。借助二代测序发现了潜在的生物标志物和治疗靶点；还证实了DNA损伤修复（DDR）基因改变与高肿瘤突变负荷之间的相关性。
