DOI QR코드

DOI QR Code

A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase

  • Yu, Su Jong (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Won, Jae-Kyung (Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Ryu, Han Suk (Department of Pathology, Seoul National University College of Medicine) ;
  • Choi, Won-Mook (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Cho, Hyeki (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Cho, Eun-Ju (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Lee, Jeong-Hoon (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Kim, Yoon Jun (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Suh, Kyung-Suk (Department of Surgery, Seoul National University College of Medicine) ;
  • Jang, Ja-June (Department of Pathology, Seoul National University College of Medicine) ;
  • Kim, Chung Yong (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Lee, Hyo-Suk (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Yoon, Jung-Hwan (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Cho, Kwang-Hyun (Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))
  • 투고 : 2014.06.15
  • 심사 : 2014.07.02
  • 발행 : 2014.09.01

초록

Background/Aims: 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.

키워드

참고문헌

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300. https://doi.org/10.3322/caac.20073
  2. Qin LX, Tang ZY. Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol 2004;130:497-513.
  3. Xu S, Sankar S, Neamati N. Protein disulfide isomerase: a promising target for cancer therapy. Drug Discov Today 2014;19:222-240. https://doi.org/10.1016/j.drudis.2013.10.017
  4. Lee HH, Lim CA, Cheong YT, Singh M, Gam LH. Comparison of protein expression profiles of different stages of lymph nodes metastasis in breast cancer. Int J Biol Sci 2012;8:353-362. https://doi.org/10.7150/ijbs.3157
  5. Goplen D, Wang J, Enger PO, et al. Protein disulfide isomerase expression is related to the invasive properties of malignant glioma. Cancer Res 2006;66:9895-9902. https://doi.org/10.1158/0008-5472.CAN-05-4589
  6. Xu S, Butkevich AN, Yamada R, et al. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A 2012;109:16348-16353. https://doi.org/10.1073/pnas.1205226109
  7. Welsh JB, Sapinoso LM, Su AI, et al. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 2001;61:5974-5978.
  8. Yu SJ, Yoon JH, Yang JI, et al. Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition. J Bioenerg Biomembr 2012;44:101-115. https://doi.org/10.1007/s10863-012-9416-5
  9. Shin E, Yu YD, Kim DS, Won NH. Adiponectin receptor expression predicts favorable prognosis in cases of hepatocellular carcinoma. Pathol Oncol Res 2014;20:667-675. https://doi.org/10.1007/s12253-014-9747-0
  10. Kee KM, Wang JH, Lin CY, Wang CC, Cheng YF, Lu SN. Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center. Dig Dis Sci 2013;58:2721-2728. https://doi.org/10.1007/s10620-013-2716-8
  11. Tager M, Kroning H, Thiel U, Ansorge S. Membrane-bound proteindisulfide isomerase (PDI) is involved in regulation of surface expression of thiols and drug sensitivity of B-CLL cells. Exp Hematol 1997;25:601-607.
  12. Sipes NJ, Miller DA, Bascom CC, Winkler JK, Matrisian LM, Moses HL. Altered regulation of protein disulfide isomerase in cells resistant to the growth-inhibitory effects of transforming growth factor beta 1. Cell Growth Differ 1990;1:241-246.
  13. Lovat PE, Corazzari M, Armstrong JL, et al. Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Res 2008;68:5363-5369. https://doi.org/10.1158/0008-5472.CAN-08-0035
  14. Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 2005;115:2656-2664. https://doi.org/10.1172/JCI26373
  15. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006;7:880-885. https://doi.org/10.1038/sj.embor.7400779
  16. Puig A, Lyles MM, Noiva R, Gilbert HF. The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase. J Biol Chem 1994;269:19128-19135.
  17. Tezuka M, Hayashi K, Kubota K, et al. Growth rate of locally recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization: comparing the growth rate of locally recurrent tumor with that of primary hepatocellular carcinoma. Dig Dis Sci 2007;52:783-788. https://doi.org/10.1007/s10620-006-9537-y
  18. Gwak GY, Yoon JH, Kim KM, Lee HS, Chung JW, Gores GJ. Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression. J Hepatol 2005;42:358-364. https://doi.org/10.1016/j.jhep.2004.11.020
  19. Rapisarda A, Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist Updat 2009;12:74-80. https://doi.org/10.1016/j.drup.2009.03.002
  20. Mujcic H, Nagelkerke A, Rouschop KM, et al. Hypoxic activation of the PERK/eIF2alpha arm of the unfolded protein response promotes metastasis through induction of LAMP3. Clin Cancer Res 2013;19:6126-6137. https://doi.org/10.1158/1078-0432.CCR-13-0526
  21. Mahadevan NR, Rodvold JJ, Zanetti M. A Janus-faced role of the unfolded protein response in antitumor immunity. Oncoimmunology 2013;2:e23901. https://doi.org/10.4161/onci.23901
  22. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol 2012;23 Suppl 8:viii6-viii9.
  23. Feng Y, Tian ZM, Wan MX, Zheng ZB. Protein profile of human hepatocarcinoma cell line SMMC-7721: identification and functional analysis. World J Gastroenterol 2007;13:2608-2614. https://doi.org/10.3748/wjg.v13.i18.2608
  24. Chignard N, Shang S, Wang H, et al. Cleavage of endoplasmic reticulum proteins in hepatocellular carcinoma: detection of generated fragments in patient sera. Gastroenterology 2006;130:2010-2022. https://doi.org/10.1053/j.gastro.2006.02.058

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