Department of Medical Oncology, Hospital Universitari Mutua Terrassa, University of Barcelona, Terrassa, Barcelona, Spain.
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, Faculty of Medicine and Health Sciences, University of Barcelona, IDIBAPS, Barcelona, Spain.
PLoS One. 2018 Nov 2;13(11):e0206542. doi: 10.1371/journal.pone.0206542. eCollection 2018.
Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer patients. Despite the benefits of CRT, its use in non-responder patients can be associated with increased toxicities and surgical resection delay. The identification of CRT response biomarkers, such as microRNAs, could improve the management of these patients. We have studied the microRNA expression in pretreatment endoscopy biopsies from rectal cancer patients treated with CRT to identify potential microRNAs able to predict CRT response and clinical outcome of these patients.
RNA from pretreatment endoscopy biopsies from 96 rectal cancer patients treated with preoperative CRT were studied. Pathological response was graded according to the tumor regression grade (TRG) Dworak classification. In the screening phase, 377 miRNAs were studied in 12 patients with extreme responses (TRG0-1 vs TRG4). The potential role as predictive biomarkers for CRT response, disease-free survival (DFS) and overall survival (OS) of the miRNAs identified in the screening phase were validated in the whole cohort.
In the screening phase, an 8-miRNAs CRT-response signature was identified: let-7b, let-7e, miR-21, miR-99b, miR-183, miR-328, miR-375 and miR-483-5p. In the validation phase, miR-21, miR-99b and miR-375 emerged as CRT response-related miRNAs while miR-328 and let-7e emerged as prognostic markers for DFS and OS. Interestingly, ROC curve analysis showed that the combination of miR-21, miR-99b and miR-375 had the best capacity to distinguish patients with maximum response (TRG4) from others.
miR-21, miR-99b and miR-375 could add valuable information for individualizing treatment in locally advanced rectal cancer patients.
术前放化疗（CRT）是局部晚期直肠癌患者的标准治疗方法。尽管 CRT 有其益处，但在无应答患者中使用可能会增加毒性和手术切除延迟。鉴定 CRT 反应生物标志物，如 microRNAs，可能会改善这些患者的管理。我们研究了接受 CRT 治疗的直肠癌患者术前内镜活检中的 microRNA 表达，以确定潜在的 microRNAs，这些 microRNAs能够预测这些患者的 CRT 反应和临床结局。
研究了 96 例接受术前 CRT 治疗的直肠癌患者术前内镜活检的 RNA。根据肿瘤消退分级（TRG）Dworak 分类对病理反应进行分级。在筛选阶段，对 12 例反应极端（TRG0-1 与 TRG4）的患者进行了 377 个 miRNA 的研究。在整个队列中验证了在筛选阶段鉴定的 miRNA 作为 CRT 反应、无病生存（DFS）和总生存（OS）的预测生物标志物的潜在作用。
在筛选阶段，鉴定出一个 8-microRNA CRT 反应特征：let-7b、let-7e、miR-21、miR-99b、miR-183、miR-328、miR-375 和 miR-483-5p。在验证阶段，miR-21、miR-99b 和 miR-375 成为与 CRT 反应相关的 miRNA，而 miR-328 和 let-7e 成为 DFS 和 OS 的预后标志物。有趣的是，ROC 曲线分析显示，miR-21、miR-99b 和 miR-375 的组合能够最好地区分具有最大反应（TRG4）的患者和其他患者。
miR-21、miR-99b 和 miR-375 可为局部晚期直肠癌患者的个体化治疗提供有价值的信息。
