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Zoheiry MM, Hasan SA, El-Ahwany E, et al. Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. Electron Physician. 2015;7(8):1626-37doi: 10.19082/1626.
Zoheiry, M. M., Hasan, S. A., El-Ahwany, E., Nagy, F. M., Taleb, H. A., Nosseir, M., Magdy, M., Meshaal, S., El-Talkawy, M. D., & Raafat, I. (2015). Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. Electronic physician, 7(8), 1626-37. https://doi.org/10.19082/1626
Zoheiry, Mona M, et al. "Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma." Electronic physician vol. 7,8 (2015): 1626-37. doi: https://doi.org/10.19082/1626
Zoheiry MM, Hasan SA, El-Ahwany E, Nagy FM, Taleb HA, Nosseir M, Magdy M, Meshaal S, El-Talkawy MD, Raafat I. Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. Electron Physician. 2015 Dec 20;7(8):1626-37. doi: 10.19082/1626. eCollection 2015 Dec. PMID: 26816590; PMCID: PMC4725417.
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Electron Physician. 2015 Dec 20;7(8):1626-37. doi: 10.19082/1626. eCollection 2015 Dec.

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma.

Electronic physician

Mona M Zoheiry, Shaimaa Aa Hasan, Eman El-Ahwany, Faten M Nagy, Hoda Abu Taleb, Mona Nosseir, Mona Magdy, Safa Meshaal, Mohamed Darwish El-Talkawy, Inas Raafat

Affiliations

  1. Department of Immunology, Theodor Bilharz Research Institute, Faculty of Medicine, Cairo University, Giza, Egypt.
  2. Environmental Department, Theodor Bilharz Research Institute, Faculty of Medicine, Cairo University, Giza, Egypt.
  3. Department of Pathology, Theodor Bilharz Research Institute, Faculty of Medicine, Cairo University, Giza, Egypt.
  4. Department of Clinical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt.
  5. Department of Gastroenterology, Theodor Bilharz Research Institute, Faculty of Medicine, Cairo University, Giza, Egypt.

PMID: 26816590 PMCID: PMC4725417 DOI: 10.19082/1626

Abstract

INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients.

METHODS: In this case-control study that was conducted in 2013-2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-β1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-β1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman's rank correlation coefficient (Spearman's rho).

RESULTS: Serum levels of TGF-β1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-β1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-β1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04).

CONCLUSION: Increased TGF-β1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients.

Keywords: Bone Morphogenic Protein (BMP)-7; Connective Tissue Growth Factor (CTGF); Liver Fibrosis; Transforming Growth Factor-Beta (TGF-β); YKL-40

References

  1. Zhonghua Gan Zang Bing Za Zhi. 2001 Jun;9(3):148-50 - PubMed
  2. Cytokine. 2002 Jan 21;17(2):108-17 - PubMed
  3. Nat Cell Biol. 2002 Aug;4(8):599-604 - PubMed
  4. Hepatol Res. 2003 May;26(1):1-9 - PubMed
  5. Nat Med. 2003 Jul;9(7):964-8 - PubMed
  6. World J Gastroenterol. 2005 Jan 28;11(4):476-81 - PubMed
  7. Clin Cancer Res. 2005 May 1;11(9):3326-34 - PubMed
  8. Clin Chem. 2006 Sep;52(9):1815-7 - PubMed
  9. Klin Med (Mosk). 2006;84(8):44-7 - PubMed
  10. Dan Med Bull. 2006 May;53(2):172-209 - PubMed
  11. Gut. 2007 May;56(5):706-14 - PubMed
  12. J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10 - PubMed
  13. Chin Med J (Engl). 2007 Feb 5;120(3):231-6 - PubMed
  14. Dig Dis Sci. 2007 Dec;52(12):3404-15 - PubMed
  15. Biochem Biophys Res Commun. 2007 Jun 1;357(2):467-73 - PubMed
  16. Am J Pathol. 2007 Jun;170(6):1942-53 - PubMed
  17. Hepatology. 2007 Oct;46(4):1257-70 - PubMed
  18. Comp Hepatol. 2007 Jul 30;6:7 - PubMed
  19. Gastroenterology. 2008 May;134(6):1655-69 - PubMed
  20. J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 1):1024-35 - PubMed
  21. Liver Transpl. 2008 Sep;14(9):1294-302 - PubMed
  22. Liver Int. 2008 Sep;28(8):1065-79 - PubMed
  23. J Hepatol. 2009 Feb;50(2):370-6 - PubMed
  24. World J Gastroenterol. 2009 May 28;15(20):2433-40 - PubMed
  25. Front Biosci (Landmark Ed). 2009 Jun 01;14:4992-5012 - PubMed
  26. Future Oncol. 2009 Sep;5(7):1065-82 - PubMed
  27. Hepatology. 2009 Dec;50(6):2007-13 - PubMed
  28. Cell. 2009 Nov 25;139(5):871-90 - PubMed
  29. Acta Ophthalmol. 2010 Sep;88(6):652-9 - PubMed
  30. Viral Immunol. 2010 Feb;23(1):71-8 - PubMed
  31. Int J Clin Exp Pathol. 2010 Jan 01;3(3):226-37 - PubMed
  32. J Glob Infect Dis. 2009 Jan;1(1):33-7 - PubMed
  33. J Clin Invest. 2010 Apr;120(4):1031-4 - PubMed
  34. Dig Dis Sci. 2010 Oct;55(10):2744-55 - PubMed
  35. Mol Cancer. 2010 May 26;9:122 - PubMed
  36. Cancer. 2010 Sep 1;116(17):4114-21 - PubMed
  37. Respir Res. 2010 Jun 23;11:85 - PubMed
  38. Gut. 2010 Oct;59(10):1401-9 - PubMed
  39. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2010 Apr;24(2):101-3 - PubMed
  40. Biomarkers. 2011 Jun;16(4):289-301 - PubMed
  41. Scand J Gastroenterol. 2011 Nov;46(11):1369-80 - PubMed
  42. World J Gastroenterol. 2011 Sep 7;17(33):3830-5 - PubMed
  43. Hepatobiliary Pancreat Dis Int. 2011 Dec;10(6):605-10 - PubMed
  44. Anticancer Res. 2012 Jan;32(1):141-5 - PubMed
  45. Mol Biol Rep. 2012 Jun;39(6):6843-50 - PubMed
  46. Hepatology. 2012 Aug;56(2):769-75 - PubMed
  47. World J Gastroenterol. 2012 May 14;18(18):2280-6 - PubMed
  48. Clin Infect Dis. 2012 Jul;55 Suppl 1:S10-5 - PubMed
  49. PLoS One. 2012;7(9):e44648 - PubMed
  50. Clin Sci (Lond). 2013 Feb;124(4):243-54 - PubMed
  51. Kidney Int. 2013 Feb;83(2):278-84 - PubMed
  52. Clin Chim Acta. 2013 Jun 5;421:126-31 - PubMed
  53. World J Gastroenterol. 2013 Mar 7;19(9):1405-15 - PubMed
  54. BMC Infect Dis. 2013 Jun 24;13:288 - PubMed
  55. Mem Inst Oswaldo Cruz. 2013 Nov;108(7):887-93 - PubMed
  56. Clin Chim Acta. 2014 Jun 10;433:111-22 - PubMed
  57. Genet Mol Res. 2014 Feb 20;13(1):1005-14 - PubMed
  58. World J Gastroenterol. 2014 Mar 21;20(11):2854-66 - PubMed
  59. PLoS One. 2014 Apr 29;9(4):e95959 - PubMed
  60. J Infect Dev Ctries. 2014 May 14;8(5):605-10 - PubMed
  61. Gastroenterology Res. 2010 Dec;3(6):262-271 - PubMed

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