MEP1A contributes to tumor progression and predicts poor clinical outcome in human hepatocellular carcinoma

Abstract

Although many staging classifications have been proposed for hepatocellular carcinoma (HCC), determining a patient's prognosis in clinical practice is a challenge due to the molecular diversity of HCC. We investigated the relationship between MEP1A, a candidate oncogene, and clinical outcomes of HCC patients; furthermore, we explored the role of MEP1A in HCC. In this report, it was demonstrated by quantitative real-time polymerase chain reaction that MEP1A messenger RNA levels were significantly elevated in HCC tumor tissues compared with matched adjacent nonneoplastic tissues and nonmalignant liver disease tissues. Immunohistochemical analyses of tissue samples from two independent groups of 394 HCC patients showed that positive expression of MEP1A in tumor cells was an independent and significant risk factor affecting survival after curative resection in both cohort 1 (hazard ratio = 2.05, 95% confidence interval 1.427-2.946; P < 0.001) and cohort 2 (hazard ratio = 1.89, 95% confidence interval 1.260-2.833; P = 0.002). Analysis of Barcelona Clinic Liver Cancer stage 0-A subgroup further showed that patients with positive MEP1A expression in tumor cells had poorer surgical prognoses than those with negative MEP1A expression in tumor cells (cohort 1 P = 0.001, cohort 2 P < 0.001). Both in vitro and in vivo assays showed that MEP1A promoted HCC cell proliferation, migration, and invasion. Further analyses found that MEP1A played an important role in regulating cytoskeletal events and induced epithelial-mesenchymal transition in HCC cells. Conclusion: MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC.