基于小 RNA 测序的粪便 microRNA 特征可准确区分结直肠癌：多中心研究结果。

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

机构信息

Italian Institute for Genomic Medicine, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Department of Computer Science, University of Turin, Turin, Italy.

出版信息

Gastroenterology. 2023 Sep;165(3):582-599.e8. doi: 10.1053/j.gastro.2023.05.037. Epub 2023 May 30.

DOI:10.1053/j.gastro.2023.05.037

PMID:37263306

Abstract

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis.

METHODS

A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples.

RESULTS

Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients.

CONCLUSIONS

Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

摘要

背景与目的

目前用于结直肠癌（CRC）筛查的粪便检测在检测早期肿瘤或癌前病变方面准确性有限。在这方面，我们全面评估了粪便微小 RNA（miRNA）谱作为非侵入性 CRC 诊断的生物标志物。

方法

在多个生物样本中进行了总共 1273 次小 RNA 测序实验。在一项横断面研究中，研究了来自意大利和捷克队列的粪便样本中的 miRNA 图谱（155 例 CRC、87 例腺瘤、96 例其他肠道疾病、141 例结肠镜阴性对照）。通过机器学习策略定义了用于癌症检测的预测 miRNA 特征，并在来自 141 例 CRC 患者和 80 例健康志愿者的额外粪便样本中进行了测试。将 miRNA 图谱与 132 例肿瘤/腺瘤与相邻黏膜、210 例血浆细胞外囊泡样本和 185 例粪便免疫化学检测剩余样本进行了比较。

结果

在两个队列中，CRC 患者粪便中 25 种 miRNA 的水平发生了改变（调整 P <.05）。包括 miR-149-3p、miR-607-5p、miR-1246、miR-4488 和 miR-6777-5p 的 5 种 miRNA 特征可区分患者与对照个体（曲线下面积[AUC]，0.86；95%置信区间[CI]，0.79-0.94），并在独立队列中得到验证（AUC，0.96；95%CI，0.92-1.00）。该特征将低/高分期肿瘤和晚期腺瘤患者与对照个体进行了分类（AUC，0.82；95%CI，0.71-0.97）。组织 miRNA 图谱与粪便样本的图谱相似，不同胃肠道疾病的粪便图谱突出显示了 CRC 中特异性失调的 miRNA。粪便免疫化学检测剩余样本中的 miRNA 图谱与保存在防腐剂缓冲液中收集的粪便样本的图谱具有良好的相关性，并且可以在腺瘤或 CRC 患者中检测到其变化。