用于检测结直肠腺瘤的血浆 microRNA panel：迈向更精确结直肠癌筛查的一步。

A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer.

机构信息

*Price Institute of Surgical Research and the Section of Colorectal Surgery, Hiram C. Polk Jr MD Department of Surgery †Department of Bioinformatics and Biostatistics, University of Louisville School of Medicine, Louisville, KY.

出版信息

Ann Surg. 2013 Sep;258(3):400-8. doi: 10.1097/SLA.0b013e3182a15bcc.

DOI:10.1097/SLA.0b013e3182a15bcc

PMID:24022433

Abstract

OBJECTIVE

The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas.

BACKGROUND

Detection of precancerous lesions such as CR adenoma is a key to reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding RNAs that regulate gene expression. Our prior work investigated the dysregulation of 5 plasma miRNAs in CRC patients. As intended, we undertook a more comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC.

METHODS

We screened for 380 plasma-miRNAs using microfluidic array technology (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated miRNAs (P < 0.05, False Discovery Rate: 5%) was then validated in a blinded cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients with CRC.

RESULTS

A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls with high accuracy [area under curve (AUC) = 0.868 (95% confidence interval [CI]: 0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR-139-3p) distinguished Stage IV CRC from controls with an [AUC = 0.896 (95% CI: 0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI: 0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively.

CONCLUSIONS

Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.

摘要

目的

本研究的主要目的是探究循环 microRNAs（miRNAs）作为结直肠（CR）腺瘤生物标志物的潜在用途。

背景

检测癌前病变，如 CR 腺瘤，是降低 CR 癌症（CRC）死亡率的关键。因此非常需要用于检测 CR 腺瘤和 CRC 的准确、非侵入性生物标志物。miRNAs 是一种非蛋白编码 RNA，可调节基因表达。我们之前的工作研究了 CRC 患者中 5 种血浆 miRNAs 的失调。正如预期的那样，我们在 CR 腺瘤和 CRC 患者中进行了更全面的血浆 miRNA 筛选研究。

方法

我们使用微流控芯片技术（Applied BioSystems）在一个包括 12 名健康对照者、9 名 CR 腺瘤患者和 20 名 CRC 患者的筛查队列中筛选了 380 种血浆 miRNA。然后，在一个包括 26 名健康对照者、16 名大腺瘤患者和 45 名 CRC 患者的盲法队列中验证了一组最失调的 miRNAs（P<0.05，错误发现率：5%）。

结果

一组 8 种血浆 miRNAs（miR-532-3p、miR-331、miR-195、miR-17、miR-142-3p、miR-15b、miR-532 和 miR-652）能够以高准确度区分息肉和对照组（曲线下面积（AUC）=0.868（95%置信区间[CI]：0.76-0.98]）。此外，一组 3 种血浆 miRNAs（miR-431、miR-15b 和 miR-139-3p）可以区分 IV 期 CRC 和对照组（AUC=0.896（95% CI：0.78-1.0））。所有 CRC 与对照组以及息肉与所有 CRC 的 miRNA 组的受试者工作特征曲线的 AUC 值分别为 0.829（95% CI：0.73-0.93）和 0.856（95% CI：0.75-0.97）。