血清中六种循环 miRNA 标志物的检测 panel 及其在结直肠癌诊断中的潜在价值。

A panel of six-circulating miRNA signature in serum and its potential diagnostic value in colorectal cancer.

机构信息

Department of Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences of Islamic Azad University, Tehran, Iran.

出版信息

Life Sci. 2020 Oct 1;258:118226. doi: 10.1016/j.lfs.2020.118226. Epub 2020 Aug 6.

DOI:10.1016/j.lfs.2020.118226

PMID:32771555

Abstract

AIM

Colorectal carcinoma (CRC) is one of the most prevalent cancers throughout the world. Circulating serum-derived microRNAs (miRNAs, miRs) can be used as non-invasive biomarkers for CRC diagnosis. This study aimed to identify a panel of six serum exosomal miRNAs as novel diagnostic biomarkers for CRC.

MAIN METHODS

Exosomes were isolated and characterized from the conditioned media of the human colon adenocarcinoma cells (HCT-116 and Caco2). Sera were isolated from peripheral blood of 45 CRC and also 45 healthy individuals. The expression levels and diagnostic value of candidate circulating miRNAs (miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a) were measured through quantitative real-time PCR. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic accuracy of selected miRNAs. The association of candidate miRNAs and clinicopathological characteristics e.g. tumor node metastasis (TNM) staging and lymph node metastasis (LNM) were further evaluated.

KEY FINDINGS

Circulating serum miR-19a, miR-20a, miR-150, and let-7a were significantly up-regulated in CRC patients, while miR-143 and miR-145 showed a significant down-regulation. The higher levels of miR-143 and miR-145 in patients with TNM stage I-II were detected, whereas miR-19a, miR-20a, miR-150, and let-7a were highly expressed in TNM stage III. The expression levels of miR-19a, miR-20a, and miR-150 were positively correlated with LNM status, while the expression levels of miR-143 and miR-145 were lower in patients with LNM. Area under the ROC curves of miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a were 0.87, 0.83, 0.75, 0.76, 0.78 and 0.71, respectively.

SIGNIFICANCE

We established a panel of six-circulating miRNA signature (i.e. miR-19a, miR-20a, miR-143, miR-145, miR-150, and let-7a) in serum as a non-invasive biomarker for CRC diagnosis. These findings confirm that serum-derived miRNAs have a strong potential to be a diagnostic biomarker for patients with CRC.

摘要

目的

结直肠癌（CRC）是全球最常见的癌症之一。循环血清衍生的 microRNAs（miRNAs，miRs）可用作 CRC 诊断的非侵入性生物标志物。本研究旨在鉴定一组六种血清外泌体 miRNAs 作为 CRC 的新型诊断生物标志物。

主要方法

从人结肠腺癌细胞（HCT-116 和 Caco2）的条件培养基中分离和表征外泌体。从 45 名 CRC 患者和 45 名健康个体的外周血中分离血清。通过定量实时 PCR 测量候选循环 miRNAs（miR-19a、miR-20a、miR-150、miR-143、miR-145 和 let-7a）的表达水平和诊断价值。应用受试者工作特征（ROC）曲线评估选定 miRNAs 的诊断准确性。进一步评估候选 miRNAs 与临床病理特征（例如肿瘤淋巴结转移（TNM）分期和淋巴结转移（LNM））的关联。

主要发现

CRC 患者血清 miR-19a、miR-20a、miR-150 和 let-7a 水平显著上调，而 miR-143 和 miR-145 水平显著下调。在 TNM 分期 I-II 的患者中检测到 miR-143 和 miR-145 水平较高，而 miR-19a、miR-20a、miR-150 和 let-7a 在 TNM 分期 III 中高表达。miR-19a、miR-20a 和 miR-150 的表达水平与 LNM 状态呈正相关，而 miR-143 和 miR-145 的表达水平在 LNM 患者中较低。miR-19a、miR-20a、miR-150、miR-143、miR-145 和 let-7a 的 ROC 曲线下面积分别为 0.87、0.83、0.75、0.76、0.78 和 0.71。