Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma
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 mechan...
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| Language: | English |
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Electronic Physician
2015-12-01
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| Series: | Electronic Physician |
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725417/ |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mona M Zoheiry |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T05:13:08Z |
| format | Article |
| id | doaj.art-b0bb907cad44438494a41e7db5549b82 |
| institution | Directory Open Access Journal |
| issn | 2008-5842 2008-5842 |
| language | English |
| last_indexed | 2024-12-18T05:13:08Z |
| publishDate | 2015-12-01 |
| publisher | Electronic Physician |
| record_format | Article |
| series | Electronic Physician |
| spelling | doaj.art-b0bb907cad44438494a41e7db5549b822022-12-21T21:19:50ZengElectronic PhysicianElectronic Physician2008-58422008-58422015-12-01781626163710.19082/1626Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular CarcinomaMona M ZoheiryShaimaa AA HasanEman El-AhwanyFaten M NagyHoda Abu TalebMona NosseirMona MagdySafa MeshaalMohamed Darwish EL-TalkawyInas RaafatIntroduction: 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725417/Liver FibrosisTransforming Growth Factor-Beta (TGF-β)Bone Morphogenic Protein (BMP)-7Connective Tissue Growth Factor (CTGF) |
| spellingShingle | 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 Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma Electronic Physician Liver Fibrosis Transforming Growth Factor-Beta (TGF-β) Bone Morphogenic Protein (BMP)-7 Connective Tissue Growth Factor (CTGF) |
| title | Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma |
| title_full | Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma |
| title_fullStr | Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma |
| title_full_unstemmed | Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma |
| title_short | Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma |
| title_sort | serum markers of epithelial mesenchymal transition as predictors of hcv induced liver fibrosis cirrhosis and hepatocellular carcinoma |
| topic | Liver Fibrosis Transforming Growth Factor-Beta (TGF-β) Bone Morphogenic Protein (BMP)-7 Connective Tissue Growth Factor (CTGF) |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725417/ |
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