Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China.
Department of Anorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China.
J Transl Med. 2023 Jun 29;21(1):421. doi: 10.1186/s12967-023-04249-6.
We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC).
We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays.
We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC.
EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).
本研究旨在评估细胞外囊泡（EV）衍生的 microRNAs（miRNAs）是否可作为高级腺瘤（AA）和结直肠癌（CRC）的生物标志物。
采用 miRNA 深度测序分析检测健康供者（HD）、AA 患者和 I-II 期 CRC 患者组血浆 EV 传递的 miRNA 谱变化。使用 TaqMan miRNA 检测对来自 HD、AA 患者和 CRC 患者的 173 份血浆样本（两个独立队列）进行检测，以鉴定候选 miRNA。采用受试者工作特征曲线（ROC）下面积（AUC）值确定候选 miRNA 诊断 AA 和 CRC 的准确性。采用 logistic 回归分析评估候选 miRNA 作为 AA 和 CRC 诊断的独立因素的相关性。采用功能测定探索候选 miRNA 在 CRC 恶性进展中的作用。
我们筛选并鉴定了 4 种有前景的 EV 传递 miRNA，包括在 AA 与 HD 组和 CRC 与 AA 组中显著上调或下调的 miR-185-5p。在两个独立队列中，miR-185-5p 是最佳潜在生物标志物，用于 AA 与 HD 诊断的 AUC 值为 0.737（队列 I）和 0.720（队列 II），用于 CRC 与 HD 诊断的 AUC 值为 0.887（队列 I）和 0.803（队列 II），用于 CRC 与 AA 诊断的 AUC 值为 0.700（队列 I）和 0.631（队列 II）。最后，我们证明了 miR-185-5p 的上调表达促进了 CRC 的恶性进展。
患者血浆中的 EV 传递 miR-185-5p 是一种很有前途的结直肠 AA 和 CRC 诊断生物标志物。
本研究方案获得中国海军军医大学长征医院伦理委员会批准（伦理号：2022SL005，中国临床试验注册中心注册号：ChiCTR220061592）。
