Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Gastroenterology, Shirakawa Kosei General Hospital, Fukushima, Japan.
Clin Transl Gastroenterol. 2021 May 12;12(5):e00356. doi: 10.14309/ctg.0000000000000356.
MicroRNAs (miRNAs) can serve as tumor biomarkers; however, their role in evaluating colorectal adenoma (CRA) is unclear. Recently, the organoid culture system enabled long-term expansion of human colon epithelium. This study aimed to examine the potential of exosomal miRNAs extracted from CRA organoids as biomarkers in the clinical liquid biopsy CRA test.
We established organoid cultures from normal colon and CRA using resected specimens. Exosomes were isolated from the conditioned medium organoids. MiRNAs were isolated from the exosomes, and their expression profiles were compared using microarray analysis. To identify miRNA candidates for liquid biopsy, we prospectively compared changes in their expression in serum and exosomes before and after endoscopic resection in 26 patients with CRA.
Seven exosomal miRNAs were overexpressed in CRA organoids: miR-4323, miR-4284, miR-1268a, miR-1290, miR-6766-3p, miR-21-5p, and miR-1246. The expression levels of 4 exosomal miRNAs (miR-4323, miR-4284, miR-1290, and miR-1246) and 2 serum miRNAs (miR-1290 and miR-1246) were significantly lower in posttreatment sera. The combined expression of 4 exosomal miRNAs could identify both CRA and large-size (>12.6 cm2) CRA with respective areas under the curve of 0.698 (95% confidence interval [CI] = 0.536-0.823) and 0.834 (95% CI = 0.660-0.929). Combinations of 2-serum miRNA expression values could identify both CRA and large-size CRA with respective area under the curves of 0.691 (95% CI = 0.528-0.817) and 0.834 (95% CI = 0.628-0.938).
We found that exosomal miRNAs derived from the CRA organoid culture could be potential diagnostic biomarkers for CRA.
MicroRNAs（miRNAs）可以作为肿瘤标志物；然而，它们在评估结直肠腺瘤（CRA）中的作用尚不清楚。最近，类器官培养系统实现了人类结肠上皮的长期扩增。本研究旨在探讨从 CRA 类器官中提取的外泌体 miRNAs 作为临床液体活检 CRA 试验生物标志物的潜力。
我们使用切除标本从正常结肠和 CRA 中建立类器官培养物。从条件培养基类器官中分离外泌体。从外泌体中分离 miRNAs，并使用微阵列分析比较其表达谱。为了确定液体活检的 miRNA 候选物，我们前瞻性地比较了 26 例 CRA 患者内镜切除前后血清和外泌体中 miRNA 表达的变化。
在 CRA 类器官中，有 7 种外泌体 miRNAs 过表达：miR-4323、miR-4284、miR-1268a、miR-1290、miR-6766-3p、miR-21-5p 和 miR-1246。治疗后血清中 4 种外泌体 miRNAs（miR-4323、miR-4284、miR-1290 和 miR-1246）和 2 种血清 miRNAs（miR-1290 和 miR-1246）的表达水平显著降低。4 种外泌体 miRNAs 的联合表达可以分别识别 CRA 和>12.6cm2 的大型 CRA，其曲线下面积分别为 0.698（95%置信区间[CI]：0.536-0.823）和 0.834（95% CI = 0.660-0.929）。2 种血清 miRNA 表达值的组合可以分别识别 CRA 和大型 CRA，其曲线下面积分别为 0.691（95% CI = 0.528-0.817）和 0.834（95% CI = 0.628-0.938）。
我们发现，源自 CRA 类器官培养的外泌体 miRNAs 可能是 CRA 的潜在诊断生物标志物。
