Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived From Organoid a Potential Diagnostic Biomarker?
Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived From Organoid a Potential Diagnostic Biomarker?
复制标题
DOI：
10.14309/ctg.0000000000000356
复制
发表时间：
2021-05-12
影响因子：
3.6
通讯作者：
Masamune A
中科院分区：
文献类型：
--
作者：
Handa T;Kuroha M;Nagai H;Shimoyama Y;Naito T;Moroi R;Kanazawa Y;Shiga H;Kakuta Y;Kinouchi Y;Masamune A
microRNA（miRNAs）可作为肿瘤生物标志物;然而，它们在评估结直肠腺瘤（CRA）中的作用尚不清楚。最近，类器官培养系统使人类结肠上皮细胞的长期扩增成为可能。本研究旨在检查从CRA类器官提取的外泌体miRNA作为临床液体活检CRA测试中的生物标志物的潜力。我们使用切除的标本建立了正常结肠和CRA的类器官培养。从条件培养基类器官中分离外泌体。从外泌体中分离miRNA，并使用微阵列分析比较它们的表达谱。为了确定用于液体活检的候选miRNA，我们前瞻性地比较了26例CRA患者内镜切除术前后其在血清和外泌体中表达的变化。在CRA类器官中过表达七种外泌体miRNA：miR-4323、miR-4284、miR-1268 a、miR-1290、miR-6766- 3 p、miR-21- 5 p和miR-1246。治疗后血清中4种外泌体miRNA（miR-4323、miR-4284、miR-1290和miR-1246）和2种血清miRNA（miR-1290和miR-1246）的表达水平显著降低。4种外泌体miRNAs的联合表达可以识别CRA和大尺寸（>12.6 cm 2）CRA，曲线下面积分别为0.698（95% CI = 0.536-0.823）和0.834（95% CI = 0.660-0.929）。2种血清miRNA表达值的组合可以识别CRA和大尺寸CRA，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）。我们发现来源于CRA类器官培养物的外泌体miRNA可能是CRA的潜在诊断生物标志物。
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.
登录
查看更多内容
影响因子：
--
作者：
Inadomi, John M.;Vijan, Sandeep;Janz, Nancy K.;Fagerlin, Angela;Thomas, Jennifer P.;Lin, Yunghui V.;Munoz, Roxana;Lau, Chim;Somsouk, Ma;El-Nachef, Najwa;Hayward, Rodney A.
通讯作者：
Hayward, Rodney A.
影响因子：
4.2
作者：
Chiba M;Kimura M;Asari S
通讯作者：
Asari S
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.1
作者：
Clancy, Cillian;Khan, Sonja;Dwyer, Roisin M.
通讯作者：
Dwyer, Roisin M.
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni