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Prognostic value of preoperative serum gamma-glutamyltranspeptidase in patients with hepatocellular carcinoma after hepatectomy

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Tumor Biology

Abstract

Gamma-glutamyltranspeptidase (γ-GGT), an oxidative stress marker, is correlated with inflammation in the extracellular hepatic microenvironment. This study aimed to evaluate the prognostic value of serum γ-GGT levels in patients with hepatocellular carcinoma (HCC) after hepatectomy. Three hundred and eight patients who underwent hepatic resection for HCC were included in the study. Preoperative serum γ-GGT levels, as well as demographic, clinical, and pathologic data, were analyzed. The optimal cutoff value of γ-GGT was 88 U/L. All patients were divided into γ-GGT ≤ 88 U/L group (n = 146) and γ-GGT > 88 U/L group (n = 162). The disease-free survival (DFS) and overall survival (OS) rates of patients in the γ-GGT > 88 U/L group were poorer than those in γ-GGT ≤ 88 U/L group. Preoperative serum γ-GGT levels, associating with gender, HBsAg status, tumor size, capsulation, tumor number, and vascular invasion, was an independent prognostic predictor of disease-free survival [hazard ratio (HR) = 1.616; 95 % confidence interval (CI), 1.223–2.135; P = 0.001] and overall survival (HR = 2.043; 95 % CI, 1.509–2.766; P < 0.001). Furthermore, γ-GGT was also associated with DFS and OS in small HCC (tumor size ≤5 cm) and alpha-fetoprotein (AFP) ≤ 200 ng/mL subgroup. In conclusion, γ-GGT is a promising and reliable prognostic biomarker in HCC patients after hepatic resection, especially for patients with small HCC or AFP ≤ 200 ng/mL.

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References

  1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–73.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:68–90.

    Article  Google Scholar 

  3. Ng KK, Lo CM, Liu CL, Poon RT, Chan SC, Fan ST. Survival analysis of patients with transplantable recurrent hepatocellularcarcinoma: implications for salvage liver transplant. Arch Surg. 2008;143:68–74.

    Article  PubMed  Google Scholar 

  4. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.

    Article  PubMed  Google Scholar 

  5. Hung HH, Chiou YY, Hsia CY, Su CW, Chou YH, Chiang JH, et al. Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas. Clin Gastroenterol Hepatol. 2011;9:79–86.

    Article  PubMed  Google Scholar 

  6. Ikeda Y, Taniguchi N. Gene expression of gamma-glutamyltranspeptidase. Methods Enzymol. 2005;401:408–25.

    Article  CAS  PubMed  Google Scholar 

  7. Pankiv S, Møller S, Bjørkøy G, Moens U, Huseby NE. Radiation-induced upregulation of gamma-glutamyltransferase in colon carcinoma cells is mediated through the Ras signal transduction pathway. Biochim Biophys Acta. 2006;1760:151–7.

    Article  CAS  PubMed  Google Scholar 

  8. Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38:263–355.

    Article  CAS  PubMed  Google Scholar 

  9. Corti A, Franzini M, Paolicchi A, Pompella A. Gamma-glutamyltransferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting. Anticancer Res. 2010;30:1169–82.

    CAS  PubMed  Google Scholar 

  10. Zhang JB, Chen Y, Zhang B, Xie X, Zhang L, Ge N, et al. Prognostic significance of serum gamma-glutamyl transferase in patients with intermediate hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Eur J Gastroenterol Hepatol. 2011;23:787–93.

    Article  PubMed  Google Scholar 

  11. Guiu B, Deschamps F, Boulin M, Boige V, Malka D, Ducreux M, et al. Serum gamma-glutamyl-transferase independently predicts outcome after transarterial chemoembolization of hepatocellular carcinoma: external validation. Cardiovasc Intervent Radiol. 2012;35:1102–8.

    Article  PubMed  Google Scholar 

  12. Ma H, Zhang L, Tang B, Wang Y, Chen R, Zhang B, et al. γ-Glutamyl-transpeptidase is a prognostic marker of survival and recurrence in radiofrequency-ablation treatment of hepatocellular carcinoma. Ann Surg Oncol. 2014;21:3084–9.

    Article  PubMed  Google Scholar 

  13. Hanigan MH, Frierson Jr HF. Immunohistochemical detection of gamma-glutamyltranspeptidase in normal human tissue. J Histochem Cytochem. 1996;44:1101–8.

    Article  CAS  PubMed  Google Scholar 

  14. Hanigan MH, Frierson Jr HF, Swanson PE, De Young BR. Altered expression of gamma-glutamyl transpeptidase in human tumors. Hum Pathol. 1999;30:300–5.

    Article  CAS  PubMed  Google Scholar 

  15. Pompella A, De Tata V, Paolicchi A, Zunino F. Expression of gamma-glutamyltransferase in cancer cells and its significance in drug resistance. Biochem Pharmacol. 2006;71:231–8.

    Article  CAS  PubMed  Google Scholar 

  16. Roomi MW, Gaal K, Yuan QX, French BA, Fu P, Bardag-Gorce F, et al. Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice. Exp Mol Pathol. 2006;81:8–14.

    Article  CAS  PubMed  Google Scholar 

  17. Fu SJ, Shen SL, Li SQ, Hua YP, Hu WJ, Liang LJ, et al. Prognostic value of preoperative peripheral neutrophilto-lymphocyte ratio in patients with HBV-associated hepatocellular carcinoma after radical hepatectomy. Med Oncol. 2013;30:721.

    Article  CAS  PubMed  Google Scholar 

  18. Shen SL, Fu SJ, Chen B, Kuang M, Li SQ, Hua YP, et al. Preoperative aspartate aminotransferase to platelet ratio is an independent prognostic factor for hepatitis B-induced hepatocellular carcinoma after hepatic resection. Ann Surg Oncol. 2014;21:3802–9.

    Article  PubMed  Google Scholar 

  19. Nagasue N. Liver resection for hepatocellular carcinoma: indications, techniques, complications, and prognostic factors. J Hepato-Biliary-Pancreat Surg. 1998;5:7–13.

    Article  CAS  Google Scholar 

  20. Soresi M, Magliarisi C, Campagna P, Leto G, Bonfissuto G, Riili A, et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res. 2003;23:1747–53.

    CAS  PubMed  Google Scholar 

  21. Johnson PJ. The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis. 2001;5:145–59.

    Article  CAS  PubMed  Google Scholar 

  22. Borud O, Mortensen B, Mikkelsen IM, Leroy P, Wellman M, Huseby NE. Regulation of gamma-glutamyltransferase in cisplatin-resistant and -sensitive colon carcinoma cells after acute cisplatin and oxidative stress exposures. Int J Cancer. 2000;88:464–8.

    Article  CAS  PubMed  Google Scholar 

  23. Mikkelsen IM, Huseby NE, Visvikis A, Moens U. Activation of the gamma-glutamyltransferase promoter 2 in the rat colon carcinoma cell line CC531 by histone deacetylase inhibitors is mediated through the Sp1-binding motif. Biochem Pharmacol. 2002;64:307–15.

    Article  CAS  PubMed  Google Scholar 

  24. Toyokuni S, Okamoto K, Yodoi J, Hiai H. Persistent oxidative stress in cancer. FEBS Lett. 1995;358:1–3.

    Article  CAS  PubMed  Google Scholar 

  25. Daubeuf S, Accaoui MJ, Pettersen I, Huseby NE, Visvikis A, Galteau MM. Differential regulation of gammaglutamyltransferase mRNAs in four human tumour cell lines. Biochim Biophys Acta. 2001;1568:67–73.

    Article  CAS  PubMed  Google Scholar 

  26. Bouman L, Sanceau J, Rouillard D, Bauvois B. Gammaglutamyl transpeptidase expression in Ewing’s sarcoma cells: up-regulation by interferons. Biochem J. 2002;364:719–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Silva IS, Ferraz ML, Perez RM, Lanzoni VP, Figueiredo VM, Silva AE. Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2004;19:314–8.

    Article  CAS  PubMed  Google Scholar 

  28. Everhart JE, Wright EC. Association of γ-glutamyltransferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV). Hepatology. 2013;57:1725–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by the National High Technology Research and Development Program of China (863 Program) (2012AA021007 and 2012AA021008), the Key Clinical Project from the Ministry of Health (2010159), the National Natural Science Foundation of China (81172039, 81373156, and 81471583), the Special Fund for Science Research by Ministry of Health (201302009), and the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

      Shunjun Fu, Zhiyong Guo & Xiaoshun He

    2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou, 510120, China

      Shunjun Fu

    3. Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

      Shaoqiang Li, Ming Kuang, Wenjie Hu, Yunpeng Hua & Baogang Peng

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    1. Shunjun Fu
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    Correspondence to Xiaoshun He or Baogang Peng.

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    Authors’ contributions

    SJF, ZYG, XSH, and BGP were the main authors of the manuscript. They were involved in the conception, design, and coordination of the study as well as in data analysis, interpretation of results, and drafting the manuscript. BGP and XSH were in charge of all experimental procedures. SQL, MK WJH, and YPH participated in the experimental procedures and revised critically the content of the manuscript. All authors contributed to the interpretation of data and critically revised the manuscript. All authors read and approved the final manuscript.

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    Shunjun Fu and Zhiyong Guo contributed equally to this work.

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    Fu, S., Guo, Z., Li, S. et al. Prognostic value of preoperative serum gamma-glutamyltranspeptidase in patients with hepatocellular carcinoma after hepatectomy. Tumor Biol. 37, 3433–3440 (2016). https://doi.org/10.1007/s13277-015-4136-1

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