Expression of ADAM8 and its clinical values in diagnosis and prognosis of hepatocellular carcinoma.

ABSTRACT

ADAM8 behaves as an active metalloprotease in vitro, hydrolyzing myelin basic protein and a variety of peptide substrates based on the cleavage sites of membrane-bound cytokines, growth factors, and receptors. Other studies have demonstrated overexpression of some ADAM family proteins in a variety of human tumors, but no report is available on the actual expression of ADAM8 and the correlation between clinicopathologic features and prognosis of hepatocellular carcinoma (HCC) patients. In this study, serum levels of ADAM8 were measured by ELISA in 126 patients with HCC, 50 patients with liver cirrhosis (LC), and 50 healthy individuals. The expression of ADAM8 in liver tissue was further studied using Western blotting in 126 patients with HCC and 50 with LC. The correlations between ADAM8 status and various clinicopathological parameters including survival were analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. The ELISA assay showed that the serum levels of ADAM8 in the HCC, LC, and healthy groups were 136.4 ± 34.5, 64.2 ± 20.1, and 63.2 ± 22.7 U/ml, respectively. Analysis of variance was used for inter-group comparison, and differences were found between the HCC group and the other two groups (both P < 0.001), while no difference was found between the LC group and the healthy group (P = 0.365). Western blotting assay showed that ADAM8 protein expression was detected in 62.7 % (79/126) HCC and in 32 % (16/50) LC tissues. Further, ADAM8 expression was associated closely with serum AFP elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that patients with ADAM8-positive tumors had a shorter postoperative survival time than those with ADAM8-negative tumors (P < 0.001). Multivariate analysis revealed that ADAM8 expression was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that the expression of ADAM8 serves as a poor prognostic biomarker for HCC. ADAM8 may be a potential target of antiangiogenic therapy for HCC.