title: Up-regulation of fibroblast growth factor 19 and its receptor associates with progression from fatty liver to hepatocellular carcinoma.
abstract: BACKGROUND
  Human fibroblast growth factor 19 (FGF19), its receptor (FGFR4) and EpCAM play an important role in cell proliferation, differentiation, motility, and overexpression have been linked to hepatocellular carcinoma (HCC). The aim of this study was to evaluate the FGF19 signals responsible for the progression of HCC arising from fatty liver.
  
  
  RESULTS
  FGF19 level was significantly increased in the HCC patients' serum compared to non-HCC controls. The IHC results demonstrated significant increases of protein expressions of FGF19, FGFR4 and EpCAM in specimens with fatty liver, NASH, cirrhosis, and HCC compared to healthy liver tissue. There was a significant positive correlation between the protein expressions (FGF19, FGFR4, and EpCAM) and histopathologic changes from FL to HCC. Furthermore, FGF19 was positively correlated with FGFR4 and with EpCAM.
  
  
  METHODS
  FGF19 protein levels in serum and tissues were determined by ELISA assay. The FGFR4, and EpCAM expression and tissue distribution were further evaluated by immunohistochemical staining in tissue array samples. FGF19, FGFR4 and EpCAM expressions between the different histologic stages of fatty liver steatohepatitis-cirrhosis-HCC carcinogenesis sequence were compared to healthy hepatic tissue.
  
  
  CONCLUSIONS
  Overexpression of FGF19/FGFR4 significantly correlated with EpCAM as a marker of hepatic cancer stem cells within the fatty liver-steatosis-cirrhosis-HCC sequence.
  
  
  CONCLUSIONS
  This is the first study to elucidate FGF19/FGFR4 signaling in favor of HCC cells developing as indicated by increased EpCAM within the carcinogenesis sequence from fatty liver to hepatocellular carcinoma. Our study has the potential to yield novel and cost effective screening strategies for HCC patients.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, 130022, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Doughtie
authors.affiliation: Department of Hepatology, Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Cui
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Xuanyi
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Harshul
authors.initials: H
authors.lastname: Pandit
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Suping
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Martin
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4
keywords: FGF19; FGFR4; cancer stem cell; hepatocellular carcinoma