2013, Number 5
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Ann Hepatol 2013; 12 (5)
Caspase recruitment domains. New potential markers for diagnosis of hepatocellular carcinoma associated with HCV in Egyptian patients
Abdel-Rahman Z, El-Kassas M, Saad Y, Bahnassy A, Seif El-Din HKS, Darweesh SK, Abdel HH, Esmat G
Language: English
References: 28
Page: 774-781
PDF size: 169.06 Kb.
ABSTRACT
Background and rational for the study. Chronic HCV is a major cause of HCC development. Caspase Recruitment
Domains (CARD) is protein modules that regulate apoptosis and play an important role in various
carcinogenesis processes, our aim is to assess the possible role of CARD9, CARD10 and Caspase only protein
(COP) in progression of liver fibrosis and pathogenesis of HCC in Egyptian chronic HCV patients.
Material
and methods. 130 patients were recruited and classified into 4 groups; I: chronic HCV, II: chronic active
hepatitis, III: liver cirrhosis, IV: HCV related HCC. Biochemical, virological studies, abdominal ultrasonography
and liver biopsy were performed. Quantitative estimation of mRNA of CARD9, CARD10 and COP gene expression
was performed by RT- PCR in liver biopsy from all patients.
Results. In HCC patients; age, AFP and
liver profile were significantly higher, HB and platelets were significantly lower (p value ‹0.01). The expression
levels of mRNA of CARD9, CARD10 and COP in liver biopsies of HCC were significantly higher than other
groups with direct correlation with age and no correlation with AFP, viral load, liver fibrosis or necroinflammatory
activity. On differentiation between HCC and non HCC patients each CARD was assessed separately
and combined, on combing the 3 CARDs, the sensitivity was 100%, specificity was 48%, positive predictive
value 47% and negative predictive value 100%.
Conclusions. CARD9, CARD10 and COP had no role in liver fibrosis
but may be involved in hepatic carcinogenesis and they could be used as markers for HCC diagnosis
and candid genes for molecular target therapy.
REFERENCES
Dienstag JL MJ. American gastroenterological association medical position statement on the management of hepatitis C. Gastroenterol 2006; 130: 225-30.
Motola-Kuba D, Zamora-Valdés D UM. Hepatocellular carcinoma. An overview. Ann Hepatol 2006; 5: 16-24.
Abdel-Aziz F, Habib M, Mohamed MK, Abdel-Hamid MGF, SM. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatol 2000; 32: 111-5.
Pawson T, Nash P. Protein-protein interactions define specificity in signal transduction. Genes Deviation 2000; 14: 1027-47.
Chu ZL, Pio F, Welsh K. A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis. J Biol Chem 2001; 276: 9239-45.
Roberts RL, Gearry RB, Allington MD, Morrin HR, Robinson BA, Frizelle FA. Caspase recruitment domain containing protein 15 mutations in patients with colorectal cancer. Can Res 2006; 66: 2532-5.
Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa] B activity. Annu Rev Immunol 2000; 18: 621-63.
Jihua CH, Xisheng L, Shengli C, Zongxian C, Guang C, Jirun PS, DW and R. BCL10 gene mutation in Hepatocellular carcinoma. J Chin Med 2001; 114: 747–51.
Wang M, Qanungo SCM. apoptosis repressor with caspase recruitment domain (ARC) is expressed in cancer cells and localizes to nuclei. FEBS 2005; 579: 2411-5.
McConnell BB, Vertino PM. Activation of Caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1. Can Res 2000; 60: 6243-7.
Ishak K, Baptista ABL. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-9.
Bruix J, Boix LSM. Focus on hepatocellular carcinoma. Can Cell 2004; 5: 215-9.
Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, et al; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona- 2000 EASL conference. J Hepatol 2001; 35: 421-30.
Salomao M, McMillen E, Lefkowitch JH. Recent advances in the classification of hepatocellular carcinoma. Diagnostic Histopathology 2012; 18: 37-45.
Zekri AR, Hassan ZK, Bahnassy AA, Sherif GM, Eldahshan D, Abouelhoda M, Ali A HM. Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus. Asian Pas J Cancer Prev 2012; 13: 5433-8.
Nakamura S, Nakamura SMT. Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma. Can 2005; 104: 1885-1193.
Soung YH, Lee JW KS. Mutational analysis of proapoptotic caspase-9 gene in common human carcinomas. APMIS 2006; 114: 292-7.
Park JY, Park JM JJ. Caspase 9 promoter polymorphisms and risk of primary lung cancer. Hum Mol Genet 2006; 15: 1963-71.
Hosgood HD, Baris DZY. Caspase polymorphisms and genetic susceptibility to multiple myeloma. Hematol Oncol 2008; 26: 148-51.
Qiu B, Wang X, Zhang P, Shi C, Zhang J, Qiu W, Wang W, et al. Association of TNF-a promoter polymorphism with the outcome of persistent HBV infection in a northeast Chinese Han population. Act Biochim Biophys Sin(Shanghai) 2012; 44: 712-8.
Kischkel FC, Lawrence DA TA. Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J Biol Chem 2001; 276: 46639-46.
Proell M, Gerlic M, Mace PD, Reed JC, Riedl SJ. The CARD plays a critical role in ASC foci formation and inflammasome signalling. Biochem J 2013; 449: 613-21.
Walter SR, Thein HH GH. Risk factors for hepatocellular carcinoma in a cohort infected with hepatitis B or hepatitis C. J Hepatol Gastroenterol 2011; 10: 1440-6.
Soliman A, Hung CH TA. Epidemiologic risk factors of hepatocellular carcinoma in a rural region of Egypt. Int J Hepatol 2010; 4: 681-90.
Abdel-Wahab M, El-Ghawalby N MM. Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepatogastroenterology 2007; 54: 157-62.
Mummadi RR, Petersen JR XS. Role of simple biomarkers in predicting fibrosis progression in HCV infection. World J Gastroenterol 2010; 16: 5705-10.
Yu MC, Chan KM LC. Alkaline Phosphatase: Does it have a Role in Predicting Hepatocellular Carcinoma Recurrence. World J Gastrointest Surg 2011; 15: 1440-9.
Chen TM, Huang PT TM. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy. Gastroenterol Hepatol 2007; 22: 669-75.