Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, China.
Cancer. 2018 Feb 15;124(4):785-796. doi: 10.1002/cncr.31062. Epub 2017 Nov 7.
Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell-free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma.
The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays.
The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR-17-5p/miR-135b, miR-92a-3p/miR135b, and miR-451a/miR-491-5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let-7b/miR-367-3p, miR-130a-3p/miR-409-3p, miR-148-3p/miR-27b, miR-148a-3p/miR-409-3p, and miR-21-5p/miR-367-3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism-related and inflammation-related pathways.
The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785-96. © 2017 American Cancer Society.
循环 microRNAs（miRNAs）作为癌症的有前途的生物标志物而出现。本研究的目的是研究循环无细胞 miRNAs 作为结直肠癌（CRC）及其前体病变结肠直肠腺瘤的生物标志物的潜力。
使用 NanoString miRNA 分析平台在 21 例 CRC 患者、19 例腺瘤患者和 21 例健康对照者的发现组中评估 800 种 miRNAs 的血清水平。使用 Fluidigm 定量聚合酶链反应检测在 34 例 CRC 患者、33 例腺瘤患者和 35 例健康对照者的验证队列中进一步检查差异表达 miRNA。
计算差异表达 miRNA 的表达值之间的比值。三种 miRNA 比值（miR-17-5p/miR-135b、miR-92a-3p/miR135b 和 miR-451a/miR-491-5p）被验证用于区分腺瘤患者和 CRC 患者与健康对照组，并且 5 种 miRNA 比值（let-7b/miR-367-3p、miR-130a-3p/miR-409-3p、miR-148-3p/miR-27b、miR-148a-3p/miR-409-3p 和 miR-21-5p/miR-367-3p）被验证用于区分 CRC 患者与腺瘤患者和健康对照组。在发现和验证组中，用于区分腺瘤患者与健康对照组的 3 种 miRNA 比值的受试者工作特征曲线下面积分别为 0.831 和 0.735。在发现和验证组中，用于区分 CRC 患者与腺瘤患者的 5 种 miRNA 比值的受试者工作特征曲线下面积分别为 0.797 和 0.732。途径分析显示，miRNA 比值调节的靶基因主要富集在代谢相关和炎症相关途径中。
本研究的数据表明，循环 miRNAs 可以区分 CRC 患者和腺瘤患者，并且可能代表 CRC 早期非侵入性检测的新型生物标志物。癌症 2018；124：785-96。©2017 年美国癌症协会。
