title: Three Gene Signature for Predicting the Development of Hepatocellular Carcinoma in Chronically Infected Hepatitis C Virus Patients.
abstract: Hepatitis C virus (HCV) is the leading cause of liver fibrosis and hepatocellular carcinoma (HCC). At present, there is no predictive biomarker for the patients at high risk of developing HCC. In this study, we examined the association between single-nucleotide polymorphisms (SNPs) in 3 innate immunity genes [2'-5'oligoadenylate synthetase 1 (OAS1) rs10774671, interleukin 28B (IL28B) rs12979860, and low molecular mass polypeptide 7 (LMP-7) at codon 49] besides cytomegalovirus (CMV) coinfection and susceptibility to HCC in genotype 4 (GT4) chronically infected Egyptian patients. SNPs were determined using restriction fragment length polymorphism analysis in DNA from HCC patients (n = 34) and compared with either controls (n = 70) or patients with early grades of liver fibrosis (n = 49). Our results demonstrated that patients bearing the genetic combination consisting of LMP-7 CA/AA [OR 4.75, 95% confidence interval (CI) 1.443-15.631, P = 0.007] and IL28B rs12979860 CT/TT (OR 6.00, 95% CI 1.603-22.455, P = 0.004) and positive for CMV viremia (OR 3.11, 95% CI 1.151-8.412, P = 0.02) were more likely to have HCC. However, OAS1 rs10774671 does not seem to contribute to the development of HCC. Binary regression analysis indicated that HCC risk significantly increases with the presence of each unfavorable genotype (LMP-7 CA/AA, IL28B rs12979860 CT/TT), when accompanied by the existence of CMV coinfection (probability of HCC risk is 0.8 for combined factors versus 0.14, 0.07, and 0.07 for individual factor IL28B, LMP-7, and CMV; respectively). These data suggest that the 2 SNPs and the coinfection in concert have potential in predicting the risk of HCC development in patients infected with HCV GT4.
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Marwa K
authors.initials: MK
authors.lastname: Ibrahim
authors.affiliation: 2 Endemic Medicine Department, Faculty of Medicine, Cairo University , Egypt .
authors.forename: Hosny
authors.initials: H
authors.lastname: Salama
authors.affiliation: 3 Clinical Pharmacy Department, Faculty of Pharmacy, Modern University for Technology and Information (MTI) , Cairo, Egypt .
authors.forename: Mohamad
authors.initials: M
authors.lastname: Abd El Rahman
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Reham M
authors.initials: RM
authors.lastname: Dawood
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Noha G
authors.initials: NG
authors.lastname: Bader El Din
authors.affiliation: 4 Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University , Beni-Suef, Egypt .
authors.forename: Heba F
authors.initials: HF
authors.lastname: Salem
authors.affiliation: 5 Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University , Beni-Suef, Egypt .
authors.forename: Mohamed E A
authors.initials: ME
authors.lastname: Abdelrahim
authors.affiliation: 2 Endemic Medicine Department, Faculty of Medicine, Cairo University , Egypt .
authors.forename: Dalia
authors.initials: D
authors.lastname: Omran
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Moataza H
authors.initials: MH
authors.lastname: Omran
authors.affiliation: 6 Medical Research Division, Biological Anthropology Department, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Khaled Helmi
authors.initials: KH
authors.lastname: El-Wakeel
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Tawfeek H
authors.initials: TH
authors.lastname: Abdelhafez
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khedr
authors.affiliation: 1 Genetic Engineering Division, Department of Microbial Biotechnology, National Research Centre , Dokki, Giza, Egypt .
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: El Awady
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000483:Alleles; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D059467:Transcriptome; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D007372:Interferons; D007378:Interleukins; D060588:LIM Domain Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C484380:PDLIM7 protein, human; C475085:OAS1 protein, human
keywords: HCC; HCV; IL28B; LMP7; OAS1; liver fibrosis