CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients

Abstract

Objective: The prognostic role of tumor biological markers (biomarkers) in predicting recurrence of hepatocellular carcinoma (HCC) was investigated in this study, the results of which may help to select appropriate candidates for liver transplantation (LT).Methods: Tissue samples from 82 HCC patients with cirrhosis who had undergone LT were immunohistochemically stained with antibodies of anti-CD147, anti-matrix metalloproteinases-2 (MMP-2), MMP-9 and anti-vascular endothelial growth factor (VEGF). Tumor microvessel density (MVD) was evaluated by using CD34. Multivariate Cox regression analysis was performed to identify the relevant prognostic factors.Results: A significant correlation was found between the expression of CD147, VEGF, MMP-2, MMP-9 and MVD-CD34 in HCC. Tumor CD147 expression (P<0.0001), tumor MVD-CD34 (P < 0.0001), MMP-9 in stromal compartment (P=0.0257) and tumor VEGF expression (P=0.0335) were significantly associated with the recurrence in HCC patients after LT. Univariate analysis showed that strong CD147 expression and high MVD-CD34 were significantly associated with poor tumor recurrence-free survival after LT (P < 0.0001). Multivariate analysis indicated that CD147 (P=0.0001), MVD-CD34 (P=0.0118), MMP-2 (P =0.0312) and MMP-9 (P =0.0280) in stromal compartment were all significant predictors in predicting HCC recurrence, while VEGF, MMP-2 and MMP-9 in tumor compartment were not significantly associated with poor prognosis.Conclusions: The tumor biomarkers CD147 and MVD-CD34 are more feasible markers for rational selection of LT candidates with HCC. MMP-9 and MMP-2 expression in stromal compartment, combined with pTNM tumor grade, may be helpful in predicting poor prognosis in HCC patients after LT.