Skip to main content

Advertisement

Log in

Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36–77 years); where males consistituted of majority of the group (88.8 %). All of patients had cirrhotic history. Fourty-six percent (n = 25) of patients had Child-Pugh Score A, 30 % (n = 16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p < 0.001). Male patients had higher serum HGF levels compared with female patients (p = 0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p = 0.05). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemogloblin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p = 0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Venepalli NK, Goff L. Targeting the HGF-cMET axis in hepatocellular carcinoma. Int J Hepatol. 2013;2013:341636. doi:10.1155/2013/341636.

    PubMed Central  PubMed  Google Scholar 

  2. Hamed MA, Ali SA. Non-viral factors contributing to hepatocellular carcinoma. World J Hepatol. 2013;5:311–22. doi:10.4254/wjh.v5.i6.311.

    PubMed Central  PubMed  Google Scholar 

  3. Milich DR. Immune response to hepatitis B virus proteins: relevance of the murine model. Semin Liver Dis. 1991;11:93–112. doi:10.1055/s-2008-1040428.

    Article  PubMed  CAS  Google Scholar 

  4. Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30:37–47. doi:10.1111/j.1365-2036.2009.04014.

    Article  PubMed  CAS  Google Scholar 

  5. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.

    Article  PubMed  Google Scholar 

  6. Malaguarnera G, Giordano M, Paladina I, Berretta M, Cappellani A, Malaguarnera M. Serum markers of hepatocellular carcinoma. Dig Dis Sci. 2010;55:2744–55. doi:10.1007/s10620-010-1184-7.

    Article  PubMed  CAS  Google Scholar 

  7. Nakamura T. Hepatocyte growth factor as mitogen, motogen and morphogen and its roles in organ regeneration. Princess Takamatsu Symp. 1994;24:195–213.

    PubMed  CAS  Google Scholar 

  8. Birchmeier C, Gherardi E. Development roles of HGF/SF andits receptor c-Met tyrosine kinase. Trends Cell Biol. 1998;8:404–10.

    Article  PubMed  CAS  Google Scholar 

  9. Tavian D, De Petro G, Benetti A, Portolani N, Giulini SM, Barlati S. u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma. Int J Cancer. 2000;87:644–9. doi:10.1002/1097-0215(20000901).

    Article  PubMed  CAS  Google Scholar 

  10. Scagliotti GV, Novello S, von Pawel J. The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev. 2013;39(7):793–801. doi:10.1016/j.ctrv.2013.02.001.

    Article  PubMed  CAS  Google Scholar 

  11. Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2. doi:10.1002/hep.24199.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Schirmacher P, Geerts A, Pietrangelo A, Dienes HP. vRogler CE. Hepatocyte growth fa.ctor/hepatopoietin A is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology. 1992;15:5–11.

    Article  PubMed  CAS  Google Scholar 

  13. Noji S, Tashiro K, Koyama E, Nohno T, Ohyama K, Taniguchi S, et al. Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. Biochem Biophys Res Commun. 1990;173:42–7.

    Article  PubMed  CAS  Google Scholar 

  14. Maher JJ. Cell-specific expression of hepatocyte growth factor in liver: upregulation in sinusoidal endothelial cells after carbon tetrachloride. J Clin Invest. 1993;91:2244–52. doi:10.1172/JCI116451.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Zhu M, Paddock GV. Expression of the hepatocyte growth factor-like protein gene in human hepatocellular carcinoma and interleukin-6-induced increased expression in hepatoma cells. Biochim Biophys Acta. 1999;1449:63–72.

    Article  PubMed  CAS  Google Scholar 

  16. Huang X, Chan HM, Zhao P, Luk J, Vande Woude G, Wong J. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11:6190–7.

    Article  PubMed  Google Scholar 

  17. Giles FJ, Vose JM, Do KA, Johnson MM, Manshouri T, Bociek G, et al. Clinical relevance of circulating angiogenic factors in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma. Leuk Res. 2004;28:595–604.

    Article  PubMed  CAS  Google Scholar 

  18. Soeki T, Tamura Y, Shinohara H, Sakabe K, Onose Y, Fukuda N. Serum hepatocyte growth factor predicts ventricular remodeling following myocardial infarction. Circ J. 2002;66:1003–7.

    Article  PubMed  CAS  Google Scholar 

  19. Matsumori A, Takano H, Obata JE, Takeda S, Tsuyuguchi N, Ono K, et al. Circulating hepatocyte growth factor as a diagnostic marker of thrombus formation in patients with cerebral infarction. Circ J. 2002;66:216–8.

    Article  PubMed  Google Scholar 

  20. Sekine K, Fujishima S, Aikawa N. Plasma hepatocyte growth factor is increased in early-phase sepsis. J Infect Chemother. 2004;10:110–4. doi:10.1007/s10156-004-0301-y.

    Article  PubMed  CAS  Google Scholar 

  21. Hata N, Matsumori A, Yokoyama S, Ohba T, Shinada T, Yoshida H, et al. Hepatocyte growth factor and cardiovascular thrombosis in patients admitted to the intensive care unit. Circ J. 2004;68:645–9.

    Article  PubMed  CAS  Google Scholar 

  22. Breuhan K, Longerich T, Schirmacher P. Dysregulation of growth factor signalling in human hepatocellular carcinoma. Oncogene. 2006;25:3787–800. doi:10.1038/sj.onc.1209556.

    Article  CAS  Google Scholar 

  23. Yamagamim H, Moriyama M, Matsumura H, Aoki H, Shimizu T, Saito T, et al. Serum concentrations of human hepatocyte growth factor is a useful indicator for predicting the occurrence of hepatocellular carcinomas in C-viral chronic liver diseases. Cancer. 2002;95:824–34. doi:10.1002/cncr.10732.

    Article  PubMed  CAS  Google Scholar 

  24. Mizuguchi T, Katsuramaki T, Nobuoka T, Kawamoto M, Oshima H, Kawasaki H, et al. Serum hyaluronate level for predicting subclinical liver dysfunction after hepatectomy. World J Surg. 2004;8:971–6. doi:10.1007/s00268-004-7389-1.

    Article  Google Scholar 

  25. Wu FS, Zheng SS, Wu LJ, Ding W, Ma ZM, Wang ZM, et al. Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma. Zhonghua Wai Ke Za Zhi. 2006;44:603.

    PubMed  Google Scholar 

Download references

Conflicts of interest

None

Source of funding

None declared

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Karabulut.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karabulut, S., Tas, F., Akyüz, F. et al. Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma. Tumor Biol. 35, 2327–2333 (2014). https://doi.org/10.1007/s13277-013-1308-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1308-8

Keywords

Navigation