Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived from Organoid a Potential Diagnostic Biomarker?

Abstract Background: MicroRNAs (miRNAs) have attracted considerable attention as tumor biomarkers. Nevertheless, few reports have described studies of colorectal adenoma (CRA) for liquid biopsy. Recently, organoid culture system development has supported the long-term expansion of investigations of human colon epithelium. This study examined the profile of exosomal miRNAs extracted from CRA organoid and potentiation of candidate miRNAs for clinical application of liquid biopsy in CRA patients. Method: We established organoids from normal colon tissues and CRA from endoscopically resected specimens. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The microRNA expression profiles were compared using microarray analysis. To investigate exosomal miRNAs extracted from organoid culture as a candidate for liquid biopsy, we prospectively compared changes in the expression of serum and exosomal miRNA before and after endoscopic resection in 26 patients with CRA.Result: We established three organoid lines from normal colon epithelium and CRA. Microarray analysis revealed that seven exosomal miRNAs expression in CRA organoids were increased compared with normal colon organoids: miR-4323, miR-4284, miR-1268a, miR-1290, miR-6766-3p, miR-21-5p, and miR-1246. The expressions of four exosomal miRNAs (miR-4323, miR-4284, miR-1290, and miR-1246) and two serum miRNAs (miR-1290 and miR-1246) were significantly lower in post-treatment sera. Combinations of four exosomal miRNA expressions can differentiate both CRA and large-size (>12.6 cm2) CRA with respective areas under the curve (AUCs) of 0.698 (95% CI = 0.536–0.823) and 0.834 (95% CI = 0.660–0.929). Combinations of two-serum miRNA expression can differentiate both CRA and large-size CRA with respective AUCs of 0.691 (95% CI = 0.528–0.817) and 0.834 (95% CI = 0.628–0.938). Conclusion: This report is the first to show that exosomal miRNAs derived from CRA organoid culture have potential for use as diagnostic biomarkers for CRA.