SIGNIFICANCE OF SERUM miR-10b-3p IN PREDICTING PRESENCE OF MICROVASCULAR INVASION OF HEPATOCELLULAR CARCINOMA (HCC)

초록

Background and Aims: Analyzing miRNA expression in the easily accessible serum is meaningful in the prediction of prognosis in HCC patients. Over-expression of tissue miR-10b is reported to be related to HCC invasion in previous study. We aimed to demonstrate the clinical implication of serum miR-10b-3p expression in the prediction of microvascular invasion which was not evident in the pre-operative imaging studies. Methods: Among the 248 HCC patients who underwent curative resection between 2005 and 2013, 58 patients who did not show macrovascular invasion in the pre-operative images were analyzed. The expressions of serum miR-10b-3p were compared between the groups of patients either with (n = 22) or without (n = 36) the presence of microvascular invasion (miVI) in the resected specimens. Also, we transfected miR-10b-3p inhibitor in SNU-475 cells and evaluated the invasive activity of cells and changes in PTEN protein levels by western blot analysis. Results: Baseline characteristics of the two groups were comparable except the better differentiation of the tumor in the patients without miVI (p = 0.027). The expression of serum miR-10b-3p was up-regulated in the patient group with miVI, and the fold change was 1.8 (IQR 0.4–5.0, p = 0.002). The introduction of miR-10b-3p inhibitor into SNU-475 cells showed the decrease of invasion activity by 30% (1.0 vs. 0.7, p = 0.029). PTEN protein level was higher in the miR-10b-3p inhibitor-transfected cells when it is compared to the un-transfected cells (fold change 1.6). Conclusions: Over-expression of serum miR-10b-3p targeting PTEN was related to the vascular invasion of HCC which was not detected by conventional imaging modalities.