TY - JOUR
T1 - Liquid Biopsy for Colorectal Adenoma
T2 - Is the Exosomal miRNA Derived from Organoid a Potential Diagnostic Biomarker?
AU - Handa, Tomoyuki
AU - Kuroha, Masatake
AU - Nagai, Hiroshi
AU - Shimoyama, Yusuke
AU - Naito, Takeo
AU - Moroi, Rintaro
AU - Kanazawa, Yoshitake
AU - Shiga, Hisashi
AU - Kakuta, Yoichi
AU - Kinouchi, Yoshitaka
AU - Masamune, Atsushi
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/5/12
Y1 - 2021/5/12
N2 - INTRODUCTION: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.METHODS: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.RESULTS: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).DISCUSSION:We found that exosomal miRNAs derived from the CRA organoid culture could be potential diagnostic biomarkers for CRA.
AB - INTRODUCTION: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.METHODS: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.RESULTS: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).DISCUSSION:We found that exosomal miRNAs derived from the CRA organoid culture could be potential diagnostic biomarkers for CRA.
UR - http://www.scopus.com/inward/record.url?scp=85105839406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105839406&partnerID=8YFLogxK
U2 - 10.14309/ctg.0000000000000356
DO - 10.14309/ctg.0000000000000356
M3 - Article
C2 - 33979310
AN - SCOPUS:85105839406
SN - 2155-384X
VL - 12
SP - E00356
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
IS - 5
ER -