title: SERPINB3 is associated with TGF-β1 and cytoplasmic β-catenin expression in hepatocellular carcinomas with poor prognosis.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most important sanitary problems for its prevalence and poor prognosis. To date, no information is available on the prognostic value of the ov-serpin SERPINB3, detected in primary liver cancer but not in normal liver. The aim of the study was to analyse SERPINB3 expression in liver cancer in relation with molecular signatures of poor prognosis and with clinical outcome.
  
  
  METHODS
  Liver tumours of 97 patients were analysed in parallel for SERPINB3, TGF-β and β-catenin. In a subgroup of 67 patients with adequate clinical follow-up, the correlation of molecular findings with clinical outcome was also carried out.
  
  
  RESULTS
  High SERPINB3 levels were detectable in 22% of the patients. A significant correlation of this serpin with TGF-β at transcription and protein level was observed, whereas for β-catenin a strong correlation was found only at post-transcription level. These findings were in agreement with transcriptome data meta-analysis, showing accumulation of SERPINB3 in the poor-prognosis subclass (S1). High levels of this serpin were significantly associated with early tumour recurrence and high SERPINB3 was the only variable significantly associated with time to recurrence at multivariate analysis.
  
  
  CONCLUSIONS
  SERPINB3 is overexpressed in the subset of the most aggressive HCCs.
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Turato
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padua, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Fasolato
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ruvoletto
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Terrin
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Quarta
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padua, Padua, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ramirez Morales
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Biasiolo
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padua, Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zanus
authors.affiliation: Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zali
authors.affiliation: 1] Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.
authors.forename: P S
authors.initials: PS
authors.lastname: Tan
authors.affiliation: Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshida
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gatta
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padua, Padua, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Cillo
authors.affiliation: Dept of Medicine, University of Padua, Padua, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pontisso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; C495270:CTNNB1 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D015843:Serpins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; C051072:squamous cell carcinoma-related antigen