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http://dx.doi.org/10.7314/APJCP.2012.13.11.5433

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus  

Zekri, Abdel-Rahman N. (Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute)
Hassan, Zeinab K. (Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute)
Bahnassy, Abeer A. (Pathology Department, National Cancer Institute)
Sherif, Ghada M. (Biostatistic and Epidemiology Department, National Cancer Institute)
ELdahshan, Dina (Clinical Pathology Department, Faculty of Medicine, Cairo University)
Abouelhoda, Mohamed (Center of Informatics Sciences, Nile University)
Ali, Ahmed (Center of Informatics Sciences, Nile University)
Hafez, Mohamed M. (Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.11, 2012 , pp. 5433-5438 More about this Journal
Abstract
Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.
Keywords
Egyptian HCC; hepatitis C virus; gene expression profile; microarrays;
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1 Altekruse SF, McGlynn KA, Reichman ME (2009). Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975-2005. J Clin Oncol, 27, 1485-91.   DOI
2 Anwar WA, Khaled HM, Amra HA, El-Nezami H, Loffredo CA (2008). Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res, 659, 176-84.   DOI   ScienceOn
3 Castello G, Costantini S, Scala S (2010). Targeting the inflammation in HCV-associated hepatocellular carcinoma: a role in the prevention and treatment. J Transl Med, 8, 109.   DOI
4 Chang ML, Yeh CT, Chen JC, et al (2008). Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis. BMC Genomics, 9, 109.   DOI
5 Ciccaglione AR, Marcantonio C, Tritarelli E, et al (2008). Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones. BMC Genomics, 9, 309.   DOI
6 El-Serag HB, Rudolph KL (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132, 2557-76.   DOI   ScienceOn
7 Elam MB, Cowan GS, Rooney RJ, et al (2009). Hepatic gene expression in morbidly obese women: implications for disease susceptibility. Obesity (Silver Spring), 17, 1563-73.   DOI
8 Fassio E (2010). Hepatitis C and hepatocellular carcinoma. Ann Hepatol, 9, 119-22.
9 Harvey CE, Post JJ, Palladinetti P, et al (2003). Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. J Leukoc Biol, 74, 360-9.   DOI
10 Hu C, Li H, Li J, et al (2008). Analysis of ABCG2 expression and side population identifies intrinsic drug efflux in the HCC cell line MHCC-97L and its modulation by Akt signaling. Carcinogenesis, 29, 2289-97.   DOI
11 Kao JH, Chen PJ, Lai MY, Chen DS (2002). Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol, 40, 4068-71.   DOI
12 Prasanthi JR, Huls A, Thomasson S, et al (2009). Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegener, 4, 1.   DOI
13 Kapadia SB, Chisari FV (2005). Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA, 102, 2561-6.   DOI
14 London WT, Evans AA, McGlynn K, et al (1995). Viral, host and environmental risk factors for hepatocellular carcinoma: a prospective study in Haimen City, China. Intervirology, 38, 155-61.   DOI
15 McGivern DR, Lemon SM (2011). Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer. Oncogene, 30, 1969-83.   DOI   ScienceOn
16 Ryder SD (2003). Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut, 52, 1-8.   DOI   ScienceOn
17 Singh R, Kaushik S, Wang Y, et al (2009). Autophagy regulates lipid metabolism. Nature, 458, 1131-5.   DOI
18 Su AI, Pezacki JP, Wodicka L, et al (2002). Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci USA, 99, 15669-74.   DOI
19 Wang K, Song Y, Chen DB, Zheng J (2008). Protein phosphatase 3 differentially modulates vascular endothelial growth factorand fibroblast growth factor 2-stimulated cell proliferation and signaling in ovine fetoplacental artery endothelial cells. Biol Reprod, 79, 704-10.   DOI
20 Wang S, Tang H, He F, et al (2006). On the role of liver-enriched transcription factors in regulating HBV transcription and replication. Sichuan Da Xue Xue Bao Yi Xue Ban, 37, 35-9.
21 Zekri AR, Bahnassy AA, Shaarawy SM, et al (2000). Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the development of hepatocellular carcinoma. J Med Microbiol, 49, 89-95.   DOI
22 Yamashita T, Honda M, Kaneko S (2011). Molecular mechanisms of hepatocarcinogenesis in chronic hepatitis C virus infection. J Gastroenterol Hepatol, 26, 960-4.   DOI
23 Yu MC, Yuan JM (2004). Environmental factors and risk for hepatocellular carcinoma. Gastroenterology, 127, 72-8.   DOI   ScienceOn
24 Zekri AR, Bahnassy AA, Abdel-Wahab SA, et al (2009). Expression of pro-and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4. J Gastroenterol Hepatol, 24, 416-28.   DOI   ScienceOn
25 Zekri AR, Hafez MM, Bahnassy AA, et al (2008). Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus Genotype 4 by 15 K cDNA microarray: preliminary study. BMC Res Notes, 1, 106.   DOI
26 Zen Y, Fujii T, Yoshikawa S, et al (2007). Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol, 170, 1750-62.   DOI