Abstract
BackgroundAfter surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. Consequently, we examined the expression pattern and prognostic value of miR-19b in samples from these patients.MethodsWe performed a miRNA microarray to detect differential expression of microRNAs (miRNAs) in 5 paired samples of HCC and non-tumoral adjacent liver tissue and a quantitative real-time polymerase chain reaction (PCR) analysis to validate the results in 81 paired samples of HCC and adjacent non-tumoral liver tissues. We examined the associations of miR-19b expression with clinicopathological parameters and survival. MiR-19b was knocked down in Hep3B and an mRNA microarray was performed to detect the affected genes.ResultsIn both the miRNA microarray and real-time PCR, miR-19b was significantly overexpressed in the HCC tumor compared with adjacent non-tumor liver tissues (P < 0.001). The expression of miR-19b was significantly higher in patients who were disease-free 2 years after surgery (P < 0.001). High miR-19b expression levels were associated with higher α-fetoprotein levels (P = 0.017). In the log-rank test, high miR-19b was associated with better disease-free survival (median survival 37.107 vs. 11.357; P = 0.022). In Cox multivariate analysis, high miR-19b predicted better disease-free survival and overall survival (hazards ratio [HR] = 0.453, 95 % confidence interval [CI] = 0.245–0.845, P = 0.013; HR = 0.318, CI = 0.120–0.846, P = 0.022, respectively). N-myc downstream regulated 1 (NDRG1) was downregulated, while epithelial cell adhesion molecule (EPCAM), hypoxia-inducible factor 1-alpha (HIF1A), high-mobility group protein B2 (HMGB2), and mitogen activated protein kinase 14 (MAPK14) were upregulated when miR-19b was knocked down in Hep3B.ConclusionsThe overexpression of miR-19b was significantly correlated with better disease-free and overall survival in patients with HCC presenting with vascular invasion or multifocal disease after curative surgery. MiR-19b may influence the expression of NDRG1, EPCAM, HMGB2, HIF1A, and MAPK14.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1671-5) contains supplementary material, which is available to authorized users.
Highlights
After surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery
We investigated the feasibility of miR-19b as a novel prognostic factor for hepatitis B virus (HBV)-associated HCC with multifocal disease or vascular invasion after curative surgery
Overexpression of miR-19b in hepatocellular carcinoma We first performed a miRNA microarray for 5 selected paired HCC and adjacent non-tumoral liver tissue samples
Summary
After surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. We examined the expression pattern and prognostic value of miR-19b in samples from these patients. Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide, and the third most common cause of cancer-related deaths [1]. Surgical resection of the tumor remains one of the most effective ways to cure HCC. Several reports have shown that curative surgery provides benefits even in patients with vascular invasion or multifocal diseases [4, 5]. Risk stratification of patients receiving surgery and identification of high-risk groups are major challenges. Prognostic factors focusing on this group of patients have been limited
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