Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients

Biomarkers. 2011 Jun;16(4):346-54. doi: 10.3109/1354750X.2011.573095. Epub 2011 Apr 20.

Abstract

Background/aim: 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.

Patients/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.

Conclusion: 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.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor II / analysis*
  • Liver Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Matrix Metalloproteinases / blood
  • Middle Aged
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-1 / blood*

Substances

  • Biomarkers, Tumor
  • Tissue Inhibitor of Metalloproteinase-1
  • Insulin-Like Growth Factor II
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9