Lower expression of tumor microRNA-26a is associated with higher recurrence in patients with hepatocellular carcinoma undergoing surgical treatment

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) exhibit lower tumor microRNA-26a (miR-26a) expression which is associated with worse outcomes. It is unknown if similar miR-26a loss occurs in HCC developed in other liver diseases. We examined tumor miR-26a expression and its impact on recurrence and mortality in a North American HCC cohort. METHODS: MiR-26a levels from tumor and surrounding nontumor liver tissue in 186 subjects were collected. We defined lower tumor expression of miR-26a as <1-fold that of the adjacent nontumor liver tissue. RESULTS: Viral hepatitis (42%; 40% hepatitis C and 2% HBV), alcohol (19%), and nonalcoholic fatty liver disease (NAFLD) (18%) were the most common causes of liver disease. The prevalence of lower tumor miR-26a expression was 68%, and it was evident in HCCs arising in all etiologies (viral hepatitis 60%, alcohol 61%, and NAFLD 76%). Subjects with lower tumor miR-26a expression had significantly higher tumor recurrence (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.18 to 5.1; P = 0.016) and higher mortality of borderline significance (HR, 1.51; 95% CI, 0.94 to 2.41; P = 0.086). CONCLUSION: Reduced miR-26a expression is a common phenomenon in HCC arising in North American patients with different underlying liver diseases and may increase recurrence and mortality after surgery.