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

• Enrollment of patients with HCC underwent chemoembolization
• Evaluation of serum concentrations of MMP-2 and TIMP-2 at three follow-up time points
• Comparison of MMP-2/TIMP-2 balance and response to TACE treatment in the follow-up

Background and aimsTrans-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.MethodsMMP-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.ResultsThe mean serum MMP-2 and TIMP-2 levels of HCC patients before TACE were 1700 ± 71 ng/mL and 89 ± 45 ng/mL respectively, significantly higher than that of the control group: 771 ± 60 ng/mL (p < 0.0001, t-test) and 25.7 ± 20 ng/mL respectively (p < 0.0001, t-test). A significant decrease of MMP-2 levels after 1 and 3 months 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 > 1500 ng/mL (median value) had worse overall and recurrence-free survival compared with those with serum MMP-2 levels < 1500 ng/mL before treatment.ConclusionHigher serum MMP-2 levels and MMP-2/TIMP-2 ratio could predict poor prognosis after TACE, suggesting prognostic role of these biomarkers in HCC.