Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a prospective prognostic indicator.

Abstract

This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model. This finding indicates that elevated levels of miR-192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients.