循环血浆 microRNAs 作为结直肠腺瘤检测的筛选方法。

Circulating plasma microRNAs as a screening method for detection of colorectal adenomas.

机构信息

University of Leicester, University Hospitals Leicester, Leicester, UK.

University of Leicester, Leicester, UK.

出版信息

Lancet. 2015 Feb 26;385 Suppl 1:S100. doi: 10.1016/S0140-6736(15)60415-9.

DOI:10.1016/S0140-6736(15)60415-9

PMID:26312830

Abstract

BACKGROUND

MicroRNAs (miRNAs) are small non-coding RNA molecules. Reduced or increased levels of specific miRNAs are observed in colon and other cancers, supporting their role in carcinogenesis. Detection of colorectal polyps is the cornerstone of the Bowel Cancer Screening Programme in the UK. However, uptake of screening nationally remains under 60%. We aimed to see whether circulating plasma miRNAs can be used to screen for patients with colorectal polyps, adenomas, or both.

METHODS

Blood samples were taken from patients from the Bowel Cancer Screening Programme (asymptomatic but faecal occult blood testing [FOBt] positive). Plasma RNA was extracted, target miRNAs (19a, 98, 146b, 186, 191, 222*, 331-5p, 452, 625, 664, 1247) were identified on pooled case miRNA assay cards, and miRNA fraction was quantified by quantitative RT-PCR assay. Results were compared with endoscopy reports and with histology of any polyps identified and removed. Analysis was done with Excel (2011) and SPSS (version 20) software.

FINDINGS

210 patients were included (117 with polyps, 12 with cancer, 81 healthy controls [FOBt positive]). The miRNA panel showed significant differences in expression (on t testing) for patients compared with controls for those with polyps, cancer, or both (miR-19a, p=0·0184; miR-98, p=0·0206; miR-146b, p=0·0029; miR-186, p=0·0006; miR-62,5 p=0·0008), polyps (miR-19a, p=0·0233; miR-98, p=0·0224; miR-146b, p=0·003; miR-186, p=0·0004; miR-625, p=0·001), adenomas (miR-19a, p=0·0339; miR-98, p=0·0266; miR-146b, p=0·0045; miR-186, p=0·0008; miR-625, p=0·0049), multiple adenomas (both sides of colon; miR-146b, p=0·0194; miR-186, p=0·0226; miR-625, p=0·0013), and right-sided adenomas (miR-98, p=0·031; miR-146b, p=0·0076; miR-186, p=0·0041; miR-331-5p, p=0·0142; miR-625, p=0·0049). Receiver operating characteristic analysis showed sensitivity of 60% or more, and specificity of 86% or more for men with polyps, men with adenomas, all patients with haemorrhoids or diverticulosis and polyps, and all patients with haemorrhoids or diverticulosis and adenomas.

INTERPRETATION

The target miRNAs that we identified showed significant differences in expression levels for patients with polyps and patients with adenomas from controls. Use of this panel has potential as a screening test.

FUNDING

Bowel Disease Research Foundation.

摘要

背景

微小 RNA（miRNA）是小的非编码 RNA 分子。在结肠癌和其他癌症中观察到特定 miRNA 的水平降低或升高，支持其在癌症发生中的作用。结直肠息肉的检测是英国结直肠癌筛查计划的基石。然而，全国范围内的参与率仍低于 60%。我们旨在研究循环血浆 miRNA 是否可用于筛查结直肠息肉、腺瘤或两者均有的患者。

方法

从参加结直肠癌筛查计划的患者（无症状但粪便潜血试验[FOBt]阳性）中抽取血样。提取血浆 RNA，在混合病例 miRNA 检测卡上鉴定目标 miRNA（19a、98、146b、186、191、222*、331-5p、452、625、664、1247），并通过定量 RT-PCR 检测定量 miRNA 分数。将结果与内镜报告以及任何已识别和切除的息肉的组织学进行比较。使用 Excel（2011）和 SPSS（版本 20）软件进行分析。

结果

纳入 210 例患者（息肉 117 例，癌症 12 例，健康对照组[FOBt 阳性]81 例）。与对照组相比，miRNA 谱在息肉、癌症或两者均有的患者中显示出显著的表达差异（t 检验）（miR-19a，p=0.0184；miR-98，p=0.0206；miR-146b，p=0.0029；miR-186，p=0.0006；miR-625，p=0.0008）、息肉（miR-19a，p=0.0233；miR-98，p=0.0224；miR-146b，p=0.003；miR-186，p=0.0004；miR-625，p=0.001）、腺瘤（miR-19a，p=0.0339；miR-98，p=0.0266；miR-146b，p=0.0045；miR-186，p=0.0008；miR-625，p=0.0049）、多发性腺瘤（结肠双侧；miR-146b，p=0.0194；miR-186，p=0.0226；miR-625，p=0.0013）和右侧腺瘤（miR-98，p=0.031；miR-146b，p=0.0076；miR-186，p=0.0041；miR-331-5p，p=0.0142；miR-625，p=0.0049）。受试者工作特征分析显示，对于男性有息肉、男性有腺瘤、所有有痔或憩室病和息肉的患者、所有有痔或憩室病和腺瘤的患者，敏感性为 60%或更高，特异性为 86%或更高。