Cancer Research Division, Cancer Council New South Wales, Sydney, Australia.
Discipline of Surgery, College of Medicine and Public Health, Flinders University of South Australia, Adelaide, SA, Australia.
Ann Surg Oncol. 2018 Sep;25(9):2731-2738. doi: 10.1245/s10434-018-6626-z. Epub 2018 Jul 9.
Clinical trials report improved overall survival following neoadjuvant chemoradiotherapy in patients undergoing surgery for esophageal adenocarcinoma, with a 10-15% survival improvement. MicroRNAs (miRNAs) are small noncoding RNAs that are known to direct the behavior of cancers, including response to treatment. We investigated the ability of miRNAs to predict outcomes after neoadjuvant chemoradiotherapy.
Endoscopic biopsies from esophageal adenocarcinomas were obtained before neoadjuvant chemoradiotherapy and esophagectomy. miRNA levels were measured in the biopsies using next generation sequencing and compared with pathological response in the surgical resection, and subsequent survival. miRNA ratios that predicted pathological response were identified by Lasso regression and leave-one-out cross-validation. Association between miRNA ratio candidates and relapse-free survival was assessed using Kaplan-Meier analysis. Cox regression and Harrell's C analyses were performed to assess the predictive performance of the miRNAs.
Two miRNA ratios (miR-4521/miR-340-5p and miR-101-3p/miR-451a) that predicted the pathological response to neoadjuvant chemoradiotherapy were found to be associated with relapse-free survival. Pretreatment expression of these two miRNA ratios, pretreatment tumor differentiation, posttreatment AJCC histopathological tumor regression grading, and posttreatment tumor clearance/margins were significant factors associated with survival in Cox regression analysis. Multivariate analysis of the two ratios together with pretherapy factors resulted in a risk prediction accuracy of 85% (Harrell's C), which was comparable with the prediction accuracy of the AJCC treatment response grading (77%).
miRNA-ratio biomarkers identified using next generation sequencing can be used to predict disease free survival following neoadjuvant chemoradiotherapy and esophagectomy in patients with esophageal adenocarcinoma.
临床研究报告显示，接受新辅助放化疗的食管腺癌患者在手术后总体生存率提高，提高了 10-15%。微小 RNA（miRNA）是一种已知可指导癌症行为的小非编码 RNA，包括对治疗的反应。我们研究了 miRNA 预测新辅助放化疗后结局的能力。
在新辅助放化疗和食管切除术前行食管腺癌内镜活检。使用下一代测序测量活检中的 miRNA 水平，并与手术切除的病理反应和随后的生存情况进行比较。通过 Lasso 回归和留一法交叉验证确定预测病理反应的 miRNA 比值。使用 Kaplan-Meier 分析评估 miRNA 比值候选物与无复发生存率之间的关系。使用 Cox 回归和 Harrell 的 C 分析评估 miRNA 的预测性能。
发现两种 miRNA 比值（miR-4521/miR-340-5p 和 miR-101-3p/miR-451a）可预测新辅助放化疗的病理反应，与无复发生存率相关。这两种 miRNA 比值的预处理表达、预处理肿瘤分化、治疗后 AJCC 组织病理学肿瘤消退分级和治疗后肿瘤清除/边缘状态是 Cox 回归分析中与生存相关的显著因素。多变量分析两种比值与治疗前因素相结合可得出 85%（Harrell 的 C）的风险预测准确率，与 AJCC 治疗反应分级的预测准确率（77%）相当。
使用下一代测序鉴定的 miRNA 比值生物标志物可用于预测接受新辅助放化疗和食管切除术的食管腺癌患者的无病生存率。
