Our recent study observed that the expression of Musashi-2 (MSI2), a member of the Musashi family, was up-regulated in hepatitis B virus (HBV) related hepatocellular carcinoma parenchymal cells. Using quantitative PCR, tissue microarray (TMA) and immunohistochemical staining, we evaluated MSI2 mRNA and protein levels in tumor tissues from patients with different stages of hepatocellular carcinoma with paired adjacent noncancerous sample sets. The following techniques were used to further investigate MSI2 function and its potential molecular mechanism: RNAi, wound healing assay, Transwell assay, quantitative PCR and western blot analysis. Immunohistochemical detection of MSI2 on a TMA containing 106 paired specimens showed that increased cytoplasmic and nuclear MSI2 staining was significantly associated with tumor size, tumor differentiation, recurrence, TNM stage, vessel invasion and Ki-67 proliferative index. Patients with MSI2-positive tumors had a significantly higher disease recurrence rate and poorer survival than patients with MSI2-negative tumors after radical surgery. Based on univariate analysis, MSI2 expression showed an unfavorable influence on both disease-free survival and overall survival. Multivariate analysis revealed that higher MSI2 expression, together with tumor size, tumor differentiation, tumor thrombus, and Ki-67 expression were independent predictors of overall survival. With MSI2 knockdown, hepatoma cell migration and invasion were inhibited and the expression of β-catenin, T cell factor (TCF) and lymphoid enhancer factor (LEF) were dysregulated. Thus, we propose that MSI2 may predict unfavorable outcomes in hepatitis B virus related hepatocellular carcinoma and promote cancer progression via the Wnt/β-catenin signaling pathway.
Keywords: Musashi-2; Wnt/β-catenin pathway; hepatocellular carcinoma; progression; tissue microarray.