Prognostic value of ADAM17 in human gastric cancer

A disintegrin and metalloproteinase-17 (ADAM17, also named as tumor necrosis factor-alpha-converting enzyme) is a member of the ADAM family. Of all ADAMs, the strongest evidence for a role in malignancy exists for ADAM17. Especially, it has been demonstrated that ADAM17 expression was significantly increased in human gastric cancer. The aim of this study was to investigate the association between ADAM17 expression and the clinicopathological features of patients with gastric cancer. The expression of ADAM17 was detected by real-time quantitative RT-PCR in gastric cancer and adjacent non-cancerous tissues. In addition, ADAM17 expression was analyzed by immunohistochemistry in 220 clinicopathologically characterized gastric cancer cases. The expression levels of ADAM17 mRNA and protein in gastric cancer tissues were both significantly higher than those in non-cancerous gastric mucosa. In addition, positive expression of ADAM17 correlated with the degree of tumor differentiation, depth of invasion, lymph node metastases, distant metastases, and TNM stage (all P<0.05). Furthermore, multivariate analysis suggested that lymph node metastases, distant metastases, TNM stage, and ADAM17 expression were independent prognostic indicators for gastric cancer. Our data suggest for the first time that the increased expression of ADAM17 in gastric cancer is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of gastric cancer.