title: Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus Genotype 4 by 15 K cDNA microarray: preliminary study.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a preventable disease rather than a curable one, since there is no well-documented effective treatment modality until now, making the molecular study of this disease mandatory.
  
  
  RESULTS
  We studied gene expression profile of 17 Egyptian HCC patients associated with HCV genotype-4 infection by c-DNA microarray. Out of the 15,660 studied genes, 446 were differentially expressed; 180 of them were up regulated and 134 were down regulated. Seventeen genes out of the 180 up-regulated genes are involved in 28 different pathways. Protein phosphatase 3 (PPP3R1) is involved in 10 different pathways followed by fibroblast growth factor receptor 1 (FGFR1), Cas-Br-M ecotropic retroviral transforming sequence b (CBLB), spleen tyrosine kinase (SYK) involved in three pathways; bone morphogenetic protein 8a (BMP8A), laminin alpha 3 (LAMA3), cell division cycle 23 (CDC23) involved in 2 pathways and NOTCH4 which regulate Notch signaling pathway. On the other hand, 25 out of the 134 down-regulated genes are involved in 20 different pathways. Integrin alpha V alpha polypeptide antigen CD51 (ITGVA) is involved in 4 pathways followed by lymphotoxin alpha (TNF superfamily, member 1) (LTA) involved in 3 pathways and alpha-2-macroglobulin (A2M), phosphorylase kinase alpha 2-liver (PHKA2) and MAGI1 membrane associated guanylate kinase 1 (MAGI1) involved in 2 pathways. In addition, 22 genes showed significantly differential expression between HCC cases with cirrhosis and without cirrhosis. Confirmation analysis was performed on subsets of these genes by RT-PCR, including some up-regulated genes such as CDK4, Bax, NOTCH4 and some down-regulated genes such as ISGF3G, TNF, and VISA.
  
  
  CONCLUSIONS
  This is the first preliminary study on gene expression profile in Egyptian HCC patients associated with HCV-Genotype-4 using the cDNA microarray. The identified genes could provide a new gate for prognostic and diagnostic markers for HCC associated with HCV. They could also be used to identify candidate genes for molecular target therapy.
authors.affiliation: Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, 1st Kasr El-Aini st, Cairo, Egypt. ncizekri@yahoo.com
authors.forename: Abdel-Rahman N
authors.initials: AR
authors.lastname: Zekri
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Bahnassy
authors.forename: Zeinab K
authors.initials: ZK
authors.lastname: Hassan
authors.forename: Tarek
authors.initials: T
authors.lastname: Mansour
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Kamal
authors.forename: Hussein M
authors.initials: HM
authors.lastname: Khaled