title: A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase.
abstract: OBJECTIVE
  Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated.
  
  
  METHODS
  We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment.
  
  
  RESULTS
  PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069).
  
  
  CONCLUSIONS
  Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. ; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. ; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Won
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Han Suk
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Won-Mook
authors.initials: WM
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeki
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. ; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019704:Protein Disulfide-Isomerases
keywords: Carcinoma, hepatocellular; Endoplasmic reticulum stress; Prognosis; Protein disulfide isomerases