A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase
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 investi...
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| Published in | The Korean journal of internal medicine Vol. 29; no. 5; pp. 580 - 587 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Korea (South)
The Korean Association of Internal Medicine
01.09.2014
대한내과학회 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1226-3303 2005-6648 2005-6648 |
| DOI | 10.3904/kjim.2014.29.5.580 |
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| Abstract | 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.
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.
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).
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. |
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| AbstractList | Background/Aims: Protein disulfide isomerase (PDI) has been implicated in thesurvival and progression of some cancer cells, by compensating for endoplasmicreticulum stress by upregulating the protein-folding capacity. However, its prognosticrole in patients with hepatocellular carcinoma (HCC) has not been investigated.
Methods: We collected HCC tissues from 83 HCC patients who underwent surgicalresection for an immunohistochemical study of PDI. Overall survival (OS)was measured from the date of surgical resection until the date of death from anycause. Radiological progression was evaluated using the modified Response EvaluationCriteria in Solid Tumors in an independent radiological assessment.
Results: PDI expression was found to be increased in human HCC compared toadjacent nontumor tissues. Increased immunopositivity for PDI was associatedwith a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patientswho had undergone surgical resection for HCC showed that tumor PDI upregulationis a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) andtime to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealedthat 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 clinicopathologicalfeatures of HCC; thus, PDI might serve as an independent prognosticfactor and a potential therapeutic target for HCC patients. KCI Citation Count: 8 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. 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. 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). 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. 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.BACKGROUND/AIMSProtein 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.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.METHODSWe 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.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).RESULTSPDI 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).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.CONCLUSIONSUpregulated 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. |
| Author | Ryu, Han Suk Cho, Eun-Ju Yu, Su Jong Won, Jae-Kyung Kim, Yoon Jun Jang, Ja-June Yoon, Jung-Hwan Cho, Kwang-Hyun Cho, Hyeki Lee, Jeong-Hoon Kim, Chung Yong Lee, Hyo-Suk Choi, Won-Mook Suh, Kyung-Suk |
| AuthorAffiliation | 1 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea 2 Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea 5 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea 3 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea 4 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea |
| AuthorAffiliation_xml | – name: 4 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea – name: 5 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea – name: 1 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea – name: 2 Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea – name: 3 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea |
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| Keywords | Carcinoma, hepatocellular Prognosis Endoplasmic reticulum stress Protein disulfide isomerases |
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| SubjectTerms | Biomarkers, Tumor - metabolism Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - pathology Female Humans Kaplan-Meier Estimate Liver Neoplasms - enzymology Liver Neoplasms - pathology Male Middle Aged Original Prognosis Protein Disulfide-Isomerases - metabolism Retrospective Studies 내과학 |
| Title | A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase |
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