title: Villin 1 is a predictive factor for the recurrence of high serum alpha-fetoprotein-associated hepatocellular carcinoma after hepatectomy.
abstract: The prognostic assessment of patients with hepatocellular carcinoma (HCC) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha-fetoprotein (AFP), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose mRNA expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum AFP-associated HCC patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum AFP-associated HCC tumor tissues. In the present analysis, only VIL1 was significantly correlated with the recurrence of HCC. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of VIL1 mRNA was also correlated with high serum PIVKAII, vascular invasion (P < 0.05), poor differentiation, an advanced cancer stage (P < 0.01) and recurrence-free survival (P = 0.017). The upregulation of VIL1 mRNA was observed more frequently in the early recurrence patients as compared to the late recurrence patients. Cox regression univariate and multivariate analyses indicated that high serum AFP levels (overall survival, HR 1.675, P = 0.002; FRS, HR 1.359, P = 0.039) and Vil1 protein expression (overall survival, HR 0.253, P = 0.009; FRS, HR 0.401, P = 0.041) were independent, unfavorable prognostic factors for overall and recurrence-free survival of patients. We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC.
authors.affiliation: Departments of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Maimaiti
authors.initials: M
authors.lastname: Xieraili
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yasen
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Gulanbar
authors.initials: G
authors.lastname: Obulhasim
authors.forename: Abudureheman
authors.initials: A
authors.lastname: Mayinuer
authors.forename: Arihiro
authors.initials: A
authors.lastname: Aihara
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D012333:RNA, Messenger; C569754:VIL1 protein, human; D000509:alpha-Fetoproteins