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.
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References
Venepalli NK, Goff L. Targeting the HGF-cMET axis in hepatocellular carcinoma. Int J Hepatol. 2013;2013:341636. doi:10.1155/2013/341636.
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.
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.
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.
Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.
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.
Nakamura T. Hepatocyte growth factor as mitogen, motogen and morphogen and its roles in organ regeneration. Princess Takamatsu Symp. 1994;24:195–213.
Birchmeier C, Gherardi E. Development roles of HGF/SF andits receptor c-Met tyrosine kinase. Trends Cell Biol. 1998;8:404–10.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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
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DOI: https://doi.org/10.1007/s13277-013-1308-8