title: 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.
  
  
  CONCLUSIONS
  MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC.
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Han-Yue
authors.initials: HY
authors.lastname: OuYang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Proctology, The Sixth Affiliated Hospital of Sun Yat-sen University (Gastrointestinal and Anal Hospital of Sun Yat-sen University), Guangzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Ultrasound, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Ru-Hai
authors.initials: RH
authors.lastname: Zou
authors.affiliation: Department of Hepatopathy, The Eighth People's Hospital of Guangzhou, Guangzhou, P.R. China.
authors.forename: Keng
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Le
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Yong-Fa
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Rong-Ping
authors.initials: RP
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.|Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality* / Q000469:parasitology / Q000601:surgery; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D008666:Metalloendopeptidases; C053833:meprin A