TY - JOUR
T1 - Gene profiling of early and advanced liver disease in chronic hepatitis C patients
AU - Khalid, Saira Sarfraz
AU - Hamid, Saeed
AU - Siddiqui, Anwar A.
AU - Qureshi, Asaf
AU - Qureshi, Nilofer
N1 - Funding Information:
Acknowledgements We thank all the patients and the staff of the Department of Radiology and Histopathology, Aga Khan University, Pakistan for their cooperation in sample collection. We are grateful to Dr. Sreekumar and Kolbert Christopher at Mayo Clinic for their support in the performance of microarray experiments. This work was supported by a grant awarded to Saira Sarfraz by the University Research Council, Aga Khan University, Karachi, Pakistan. The micro-array experiments were supported by NIH grant GM 50870 awarded to Nilofer Qureshi.
PY - 2011/9
Y1 - 2011/9
N2 - Purpose:Strong impact of hepatitis C virus (HCV) on normal regulation of cellular processes has been reported that could have significant implications for HCV pathogenesis. We aimed to determine the altered cellular processes during HCV infection with particular reference to advanced disease stages. Methods: Liver biopsy specimens of chronic hepatitis C patients classified on histological basis as early (fibrosis stage 1-2) or advanced (fibrosis stage 3-4) HCV disease were studied using microarray technology (Affymetrix GeneChipTM System). For comparison, liver specimens from patients with non-viral hepatitis (NV-hepatitis) were also analyzed by microarray. Expression data generated were analyzed using software Genespring GX and Ingenuity Pathway analysis to find the association with biological functions. We further validated the microarray results using quantitative reverse transcriptase-polymerase chain reaction. Results: Data analysis through Genespring software revealed that in advanced HCV (A-HCV) a total of 792 genes are differentially expressed when compared to early HCV (E-HCV) and 417 genes are differentially expressed when compared to NV-hepatitis. Most of these genes are involved in cancer, cellular growth and proliferation, and tissue morphology. Real time (RT) PCR analysis confirmed the differential expression of six of these genes. Conclusion: The results of this study reflect the changes taking place during the transition from early to advanced liver fibrosis, when the liver function becomes impaired and extracellular matrix deposition increases. In addition, it showed altered expression of genes with functions in cancer development, cell growth, proliferation, and cell death that might indicate high risk of cell transformation and hepatocellular carcinoma (HCC) in A-HCV disease patients.
AB - Purpose:Strong impact of hepatitis C virus (HCV) on normal regulation of cellular processes has been reported that could have significant implications for HCV pathogenesis. We aimed to determine the altered cellular processes during HCV infection with particular reference to advanced disease stages. Methods: Liver biopsy specimens of chronic hepatitis C patients classified on histological basis as early (fibrosis stage 1-2) or advanced (fibrosis stage 3-4) HCV disease were studied using microarray technology (Affymetrix GeneChipTM System). For comparison, liver specimens from patients with non-viral hepatitis (NV-hepatitis) were also analyzed by microarray. Expression data generated were analyzed using software Genespring GX and Ingenuity Pathway analysis to find the association with biological functions. We further validated the microarray results using quantitative reverse transcriptase-polymerase chain reaction. Results: Data analysis through Genespring software revealed that in advanced HCV (A-HCV) a total of 792 genes are differentially expressed when compared to early HCV (E-HCV) and 417 genes are differentially expressed when compared to NV-hepatitis. Most of these genes are involved in cancer, cellular growth and proliferation, and tissue morphology. Real time (RT) PCR analysis confirmed the differential expression of six of these genes. Conclusion: The results of this study reflect the changes taking place during the transition from early to advanced liver fibrosis, when the liver function becomes impaired and extracellular matrix deposition increases. In addition, it showed altered expression of genes with functions in cancer development, cell growth, proliferation, and cell death that might indicate high risk of cell transformation and hepatocellular carcinoma (HCC) in A-HCV disease patients.
KW - Gene expression
KW - HCV
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=80054971709&partnerID=8YFLogxK
U2 - 10.1007/s12072-011-9252-4
DO - 10.1007/s12072-011-9252-4
M3 - Article
AN - SCOPUS:80054971709
SN - 1936-0533
VL - 5
SP - 782
EP - 788
JO - Hepatology International
JF - Hepatology International
IS - 3
ER -
