title: Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma.
abstract: OBJECTIVE
  We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role.
  
  
  METHODS
  HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle.
  
  
  RESULTS
  Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo.
  
  
  CONCLUSIONS
  GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kevin Tak Pan
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Qi Zhou
authors.initials: QZ
authors.lastname: Lian
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Chang Xian
authors.initials: CX
authors.lastname: Li
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Geng
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Chang Chun
authors.initials: CC
authors.lastname: Ling
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Yuen Yuen
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Wai Ho
authors.initials: WH
authors.lastname: Yeung
authors.affiliation: Department of Paediatrics & Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Wen Wei
authors.initials: WW
authors.lastname: Tu
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor; D005979:Glutathione Peroxidase / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000201:enzymology; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000201:enzymology; D011379:Prognosis; D011994:Recombinant Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase