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Expression of GOLM1 Correlates with Prognosis in Human Hepatocellular Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Serum Golgi membrane protein 1 (GOLM1) is a novel biomarker for hepatocellular carcinoma (HCC). However, few studies have investigated the relationship between GOLM1 protein expression and clinicopathologic features in HCC patients. The aim of this study was to investigate the expression of GOLM1 in human HCC and its correlation with clinicopathologic parameters.

Methods

Clinicopathologic data were obtained through a detailed retrospective review of the medical records of 193 patients with HCC who had undergone surgical resection between 1990 and 2006 at the Taipei Veterans General Hospital. Another 120 HCC tissue samples provided by the Taiwan Liver Cancer Network were used as validation cohort. Immunohistochemical staining was used to determine the expression of GOLM1 in archived formalin-fixed, paraffin-embedded tissue specimens.

Results

GOLM1 expression was significantly higher in resected HCC tumor tissues than in corresponding normal liver tissues (p < 0.01). After a median follow-up of 51 months, multivariate analysis showed that portal vein invasion (hazard ratio [HR], 1.515; 95 % confidence interval [95 % CI], 1.008–2.277; p = 0.046) and high GOLM1 protein expression (HR, 1.696; 95 % CI, 1.160–2.479; p = 0.006) were independent prognostic factors for poor overall survival. High GOLM1 protein expression still significantly correlates with worse overall survival as well as disease-free survival in the validation cohort (p < 0.001 and p = 0.002).

Conclusions

Overexpression of GOLM1 is associated with poor prognosis in human HCC.

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Reference

  1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–1127.

    Article  PubMed  CAS  Google Scholar 

  2. El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–1763.

    Article  PubMed  Google Scholar 

  3. Chen JG, Parkin DM, Chen QG, Lu JH, Shen QJ, Zhang BC, et al. Screening for liver cancer: results of a randomised controlled trial in Qidong, China. J Med Screen. 2003;10:204–209.

    Article  PubMed  Google Scholar 

  4. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236.

    Article  PubMed  Google Scholar 

  5. Wong LL, Limm WM, Severino R, Wong LM. Improved survival with screening for hepatocellular carcinoma. Liver Transpl. 2000;6:320–325.

    Article  PubMed  CAS  Google Scholar 

  6. Min YW, Gwak GY, Lee MW, Choi MS, Lee JH, Koh KC, et al. Clinical course of sub-centimeter-sized nodules detected during surveillance for hepatocellular carcinoma. World J Gastroenterol. 2012;18:2654–2660.

    Article  PubMed  CAS  Google Scholar 

  7. Singal AG, Conjeevaram HS, Volk ML, Fu S, Fontana RJ, Askari F, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev. 2012;21:793–799.

    Article  PubMed  Google Scholar 

  8. Oka H, Tamori A, Kuroki T, Kobayashi K, Yamamoto S. Prospective study of alpha-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma. Hepatology. 1994;19:61–66.

    Article  PubMed  CAS  Google Scholar 

  9. Giannelli G, Antonaci S. New frontiers in biomarkers for hepatocellular carcinoma. Dig Liver Dis. 2006;38:854–859.

    Article  PubMed  CAS  Google Scholar 

  10. Ozkan H, Erdal H, Tutkak H, Karaeren Z, Yakut M, Yüksel O, et al. Diagnostic and prognostic validity of Golgi protein 73 in hepatocellular carcinoma. Digestion. 2011;83:83–88.

    Article  PubMed  Google Scholar 

  11. Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010;59:1687–1693.

    Article  PubMed  CAS  Google Scholar 

  12. Li X, Wu K, Fan D. Serum Golgi Phosphoprotein two level: a better marker than alpha-fetoprotein for diagnosing early hepatocellular carcinoma. Hepatology. 2009;50:325.

    Article  PubMed  Google Scholar 

  13. Kladney RD, Bulla GA, Guo L, Mason AL, Tollefson AE, Simon DJ, et al. GP73, a novel Golgi-localized protein upregulated by viral infection. Gene. 2000;249:53–65.

    Article  PubMed  CAS  Google Scholar 

  14. Zhou Y, Li L, Hu L, Peng T. Golgi phosphoprotein 2 (GOLPH2/GP73/GOLM1) interacts with secretory clusterin. Mol Biol Rep. 2011;38:1457–1462.

    Article  PubMed  CAS  Google Scholar 

  15. Hu L, Li L, Xie H, Gu Y, Peng T. The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplasmic sequences. PloS One. 2011;6:e28207.

    Article  PubMed  CAS  Google Scholar 

  16. Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, Schwartz M, et al. Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 2007;45:938–947.

    Article  PubMed  CAS  Google Scholar 

  17. Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001;23:291–299.

    PubMed  CAS  Google Scholar 

  18. Chen MH, Yeh YC, Shyr YM, Jan YH, Chao Y, Li CP, et al. Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors. J Gastroenterol. 2013;48:101–108.

    Article  PubMed  CAS  Google Scholar 

  19. Riener MO, Stenner F, Liewen H, Soll C, Breitenstein S, Pestalozzi BC, et al. Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology. 2009;49:1602–1609.

    Article  PubMed  CAS  Google Scholar 

  20. Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002;35:1431–1440.

    Article  PubMed  CAS  Google Scholar 

  21. Sun Y, Yang H, Mao Y, Xu H, Zhang J, Li G, et al. Increased Golgi protein 73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival. J Gastroenterol Hepatol. 2011;26:1207–1212.

    Article  PubMed  CAS  Google Scholar 

  22. Ando E, Kuromatsu R, Tanaka M, Takada A, Fukushima N, Sumie S, et al. Surveillance program for early detection of hepatocellular carcinoma in Japan: results of specialized department of liver disease. J Clin Gastroenterol. 2006;40:942–948.

    Article  PubMed  Google Scholar 

  23. Shim JH, Yoon DL, Han S, Lee YJ, Lee SG, Kim KM, et al. Is serum alpha-fetoprotein useful for predicting recurrence and mortality specific to hepatocellular carcinoma after hepatectomy? A test based on propensity scores and competing risks analysis. Ann Surg Oncol. 2012;19:3687–3696.

    Article  PubMed  Google Scholar 

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Acknowledgment

This research was supported by grants from Taipei Veterans General Hospital (V102E2-007), Yen Tjing Ling Medical Foundation and Taiwan Clinical Oncology Research Foundation to M.-H. Chen and National Science Council (NSC100-2627-B-010-005), National Health Research Institutes (NHRI-EX101-10029BI), Taipei Veterans General Hospital (V102E2-006 and VGHUST101-G5-1-2), and Ministry of Education Aim for the Top University Plan (National Yang Ming University) to C. Y. Huang. We would like to thank Taiwan Liver Cancer Network (TLCN) for providing the HCC tissue samples and related clinical data (all are anonymous) for our research work. This network currently includes five major medical centers (National Taiwan University Hospital, Chang-Gung Memorial Hospital-Linko, Veteran General Hospital-Taichung, Chang-Gung Memorial Hospital -Kaohsiung, and Veteran General Hospital -Kaohsiung). TLCN is supported by grants from National Science Council since 2005 till now (NSC 100-2325 -B-182 -006) and National Health Research Institutes, Taiwan.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Ming-Huang Chen MD, PhD & Peter Mu-Hsin Chang MD, PhD

  2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Ming-Huang Chen MD, PhD, Peter Mu-Hsin Chang MD, PhD & Chi-Ying F. Huang PhD

  3. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    Yi-Hua Jan PhD & Michael Hsiao PhD

  4. Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

    Yi-Hua Jan PhD & Yung-Jen Chuang PhD

  5. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Chen Yeh MD

  6. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Hao-Jan Lei PhD & Gar-Yang Chau MD, PhD

  7. Institute of Molecular and Genomic Medicine, National Health Research Institute, Zhunan, Taiwan

    Shiu-Feng Huang PhD

  8. Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan

    Chi-Ying F. Huang PhD

Authors
  1. Ming-Huang Chen MD, PhD
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  2. Yi-Hua Jan PhD
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  3. Peter Mu-Hsin Chang MD, PhD
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  4. Yung-Jen Chuang PhD
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  5. Yi-Chen Yeh MD
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  6. Hao-Jan Lei PhD
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  7. Michael Hsiao PhD
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  8. Shiu-Feng Huang PhD
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  9. Chi-Ying F. Huang PhD
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  10. Gar-Yang Chau MD, PhD
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Corresponding authors

Correspondence to Chi-Ying F. Huang PhD or Gar-Yang Chau MD, PhD.

Additional information

Ming-Huang Chen and Yi-Hua Jan contributed equally to this work.

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Chen, MH., Jan, YH., Chang, P.MH. et al. Expression of GOLM1 Correlates with Prognosis in Human Hepatocellular Carcinoma. Ann Surg Oncol 20 (Suppl 3), 616–624 (2013). https://doi.org/10.1245/s10434-013-3101-8

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  • DOI: https://doi.org/10.1245/s10434-013-3101-8

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