Jain Mark, Kamalov David, Tivtikyan Alexander, Balatsky Alexander, Samokhodskaya Larisa, Okhobotov Dmitry, Kozlova Polina, Pisarev Eduard, Zvereva Maria, Kamalov Armais
Medical Research and Educational Center, Lomonosov Moscow State University, 119992 Moscow, Russia.
Department of Fundamental Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia.
Mol Clin Oncol. 2021 Dec;15(6):253. doi: 10.3892/mco.2021.2415. Epub 2021 Oct 8.
Telomerase reverse transcriptase (TERT) promoter mutations are the most frequent genetic events in bladder cancer (BC). The aim of the present pilot study was to evaluate the diagnostic potential of urine TERT promoter mutations-based liquid biopsy in patients with an ongoing oncological process, as well as in post-resection patients at risk of BC recurrence. A total of 60 patients were enrolled, of whom 27 patients had histologically proven BC; 23 had no signs of BC (control group); and 10 patients underwent transurethral malignancy resection 3-6 months prior to urine donation ('second look' group). Urine TERT promoter mutations were detected using Droplet Digital PCR. Receiver operating characteristic curve analysis revealed significant diagnostic power of the present approach (area under the curve: -0.768). At the cut-off value of tumor DNA fraction 0.34%, the sensitivity and specificity were 55.56 and 100%, respectively. In the positive samples, tumor DNA fraction varied significantly from 0.59 to 48.77%. In the 'second look' group, tumor DNA was detected in 4/10 patients, highlighting the possibility of BC recurrence with its fraction ranging only from 0.90 to 6.61%. Therefore, urine TERT promoter mutations-based liquid biopsy appears to be a promising tool for BC diagnosis and surveillance. The main study will include recruitment of additional patients, extension of the mutation panel, prolonged follow-up of the post-resection patients, as well as screening of industrial workers exposed to specific carcinogens.
端粒酶逆转录酶（TERT）启动子突变是膀胱癌（BC）中最常见的基因事件。本初步研究的目的是评估基于尿液TERT启动子突变的液体活检在患有持续性肿瘤疾病的患者以及有BC复发风险的术后患者中的诊断潜力。总共招募了60名患者，其中27名患者经组织学证实患有BC；23名无BC迹象（对照组）；10名患者在捐尿前3 - 6个月接受了经尿道恶性肿瘤切除术（“二次检查”组）。使用数字液滴PCR检测尿液TERT启动子突变。受试者工作特征曲线分析显示本方法具有显著的诊断能力（曲线下面积：-0.768）。在肿瘤DNA分数截断值为0.34%时，敏感性和特异性分别为55.56%和100%。在阳性样本中，肿瘤DNA分数从0.59%到48.77%有显著差异。在“二次检查”组中，10名患者中有4名检测到肿瘤DNA，突出了BC复发的可能性，其分数仅在0.90%至6.61%之间。因此，基于尿液TERT启动子突变的液体活检似乎是BC诊断和监测的一种有前景的工具。主要研究将包括招募更多患者、扩展突变检测面板、延长术后患者的随访时间以及对接触特定致癌物的产业工人进行筛查。
