ADAM-17 over-expression in gallbladder carcinoma correlates with poor prognosis of patients

The ADAMs is a multi-functional gene family of membrane proteins possessing a disintegrin and metalloprotease domain. They have potential implications for the metastasis of human tumor cells via cell adhesion and protease activities. However, no studies have yet comprehensively examined the expression of ADAMs in gallbladder carcinoma. The aim of this study was to test the hypothesis that ADAM-17 (otherwise known as tumor necrosis factor-alpha converting enzyme) is involved in the progression of gallbladder carcinoma. Two hundreds samples of gallbladder carcinoma and sixty non-cancerous gallbladder samples were used to measure the expression of total ADAM-17 by enzyme-linked immunosorbent assay, and the precursor and active forms by western blotting analysis. Expression of ADAM-17 was significantly increased in tumors with high histological grade and pT stage compared with low histological grade and pT stage tumors and was not associated with patients' gender, age, histological type, and resection margin involvement. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for gallbladder carcinoma. The current study demonstrated that the over-expression of ADAM-17 in patients with gallbladder carcinoma was linked closely with histological grade, pT stage and prognosis, and thus provides further impetus for exploiting ADAM-17 as new target for the treatment of gallbladder carcinoma.