title: Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients.
abstract: OBJECTIVE
  Elevated relative expression of insulin-like growth factor-II (IGF-II) was observed in hepatocellular carcinoma (HCC) liver tissues with a role in neovascularization and associated with poor prognosis. IGF-II is influenced by the proteolytic cleavage of IGF-binding protein 3 and by matrix metalloproteinases (MMP), which are further regulated by their tissue inhibitors tissue inhibitor of metalloprotienase-1 (TIMP-1). Our aim is to study new molecular markers for HCC.
  
  
  METHODS
  RNA was extracted from the peripheral blood for evaluating the relative expression of IGF-II, MMP-9, and TIMP-1 in correlation with clinical staging of 39 HCC patients and 15 healthy controls using TaqMan real-time PCR.
  
  
  RESULTS
  The relative expression of IGF-II and MMP-9 mRNA were significantly elevated in HCC patients compared with healthy controls; P-value <0.0001 for both. There was a significant correlation between MMP-9 and different HCC stages. On the other hand, TIMP-1 was significantly down-regulated in HCC patients; P = 0.0003 with the elevation of the IGF-II/TIMP-1 ratio. Significant correlation between TIMP-1 and HCC Stage III and Stage IV was found; P-value = 0.0138.
  
  
  CONCLUSIONS
  These results highlight the importance of profiling the expression of IGF-II, MMP-9, and TIMP-1 in the peripheral blood as prognostic molecular biomarkers in HCC.
authors.affiliation: The Molecular Pathology Research Group, German University in Cairo, Cairo, Egypt.
authors.forename: H M
authors.initials: HM
authors.lastname: El Tayebi
authors.forename: W
authors.initials: W
authors.lastname: Salah
authors.forename: I H
authors.initials: IH
authors.lastname: El Sayed
authors.forename: E M
authors.initials: EM
authors.lastname: Salam
authors.forename: A R N
authors.initials: AR
authors.lastname: Zekri
authors.forename: N
authors.initials: N
authors.lastname: Zayed
authors.forename: E S
authors.initials: ES
authors.lastname: Salem
authors.forename: G
authors.initials: G
authors.lastname: Esmat
authors.forename: A I
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1; D007335:Insulin-Like Growth Factor II; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9