Exosomal miR-200 family as serum biomarkers for early detection and prognostic prediction of cholangiocarcinoma.

ABSTRACT

Cholangiocarcinoma (CCA) is a common and lethal disease but lacks of efficient biomarkers for early detection. A previous study using CCA cell lines showed a CCA-specific exosomal microRNA profile. We aimed to verify the results in CCA patients and evaluate the potential roles of these exosomal microRNAs as serum biomarkers. Peripheral blood samples were collected from 36 CCA patients and 12 healthy controls. Twenty exosomal microRNAs were compared between CCA and control group. The diagnostic value was assessed using area under receiver operating characteristic curve (AUC). Out of 20 exosomal microRNAs, 5 significantly differentially expressed between CCA and control group. Four microRNAs in miR-200 family (miR-141-3p, miR-200a-3p, miR-200b-3p, and miR-200c-3p) showed higher AUCs than CA19-9 (0.78). MiR-200c-3p presented the best diagnostic ability with the AUC of 0.93. Furthermore, miR-200a/c-3p was positively correlated with tumor stage (P < 0.05). Patients with advance tumor stage (III-IV) showed significantly higher serum exosomal miR-200a/c-3p levels than those with early stage (I-II) (P < 0.05). In conclusion, serum exosomal miR-200 family, particularly miR-200c-3p, could be efficient biomarkers for CCA. The serum levels of exosomal miR-200a/c-3p also represented the rate of CCA progression.