title: Clinical and prognostic role of circulating MMP-2 and its inhibitor TIMP-2 in HCC patients prior to and after trans-hepatic arterial chemo-embolization.
abstract: OBJECTIVE
  Trans-hepatic arterial chemo-embolization is the most commonly used treatment for unresectable hepatocellular carcinoma. The prognostic impact of tumor biomarkers has not therefore been evaluated in this treatment. Imbalance between matrix metalloproteinase-2 and tissue inhibitor metalloproteinase-2 is considered to play an important role in extracellular matrix remodeling and degradation. Higher serum levels of MMP-2 have been shown to predict a poor prognosis and shorter overall survival in HCC after TACE. The objective of this study was to evaluate the serum levels of MMP-2 and TIMP-2 in HCC patients before and after TACE to evaluate their clinical significance and usefulness as prognostic biomarkers.
  
  
  METHODS
  MMP-2 and TIMP-2 levels were measured by ELISA in 75 HCC patients and 30 healthy controls. Sera MMP-2 and TIMP-2 were correlated with clinico-pathological features.
  
  
  RESULTS
  The mean serum MMP-2 and TIMP-2 levels of HCC patients before TACE were 1700±71ng/mL and 89±45ng/mL respectively, significantly higher than that of the control group: 771±60ng/mL (p<0.0001, t-test) and 25.7±20ng/mL respectively (p<0.0001, t-test). A significant decrease of MMP-2 levels after 1 and 3months compared to baseline time was observed (p<0.0001), while with TIMP-2 a gradual increase in serum before and after TACE (p<0.01) was detected. No significant correlation between serum MMP-2 levels and other clinico-pathological features was observed. Patients with serum MMP-2 >1500ng/mL (median value) had worse overall and recurrence-free survival compared with those with serum MMP-2 levels <1500ng/mL before treatment.
  
  
  CONCLUSIONS
  Higher serum MMP-2 levels and MMP-2/TIMP-2 ratio could predict poor prognosis after TACE, suggesting prognostic role of these biomarkers in HCC.
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy. Electronic address: antonella27@inwind.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Daniele
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Divella
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Quaranta
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Mattioli
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Porzia
authors.initials: P
authors.lastname: Casamassima
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Garrisi
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Cosimo Damiano
authors.initials: CD
authors.lastname: Gadaleta
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Gadaleta-Caldarola
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Eufemia
authors.initials: E
authors.lastname: Savino
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Maci
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Bellizzi
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Fazio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016461:Chemoembolization, Therapeutic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: HCC; MMP-2; TACE; TIMP-2