Upregulated Expression of ADAM17 Is a Prognostic Marker for Patients With Gastric Cancer

Abstract

This study was designed to evaluate the expression and prognostic significance of A Disintegrin and Metalloproteinase17 (ADAM17) protein in patients with gastric cancer. Tumor invasion and metastasis are primary causes for treatment failure or death among cancer patients. ADAM17 is a multidomain transmembrane glycoprotein involved in the release of several ligands that were shown to promote tumor formation and progression. Elevated expression of ADAM17 was detected in a number of human cancers and was associated with poor progression and prognosis of the diseases. In gastric cancer, however, the expression and prognostic significance of ADAM17 has not been fully elucidated. The expressions of ADAM17 and extracellular matrix metalloproteinase inducer (EMMPRIN), a protein implicated in tumor invasion and metastasis, were detected using the tissue microarray technique and immunohistochemical EnVision method and compared with clinicopathological parameters of patients with gastric cancer. The expressions of ADAM17 and EMMPRIN were upregulated in gastric cancer lesions compared with their expressions in adjacent non-cancerous tissues (P < 0.01). High expression of ADAM17 was detected in 35.78% (156/436) of patients with gastric cancer and positively correlated with the expression of EMMPRIN (r = 0.738, P < 0.01). ADAM17 expression was associated with a number of clinicopathological parameters including depth of invasion and TNM stage of the tumor (P < 0.05). In each TNM stage, patients with high ADAM17 expression had a longer mean survival time than those with low expression (P < 0.05). Particularly, the mean survival time of stage II gastric cancer patients with low ADAM17 expression was longer than that of stage I patients with high ADAM17 expression (P < 0.01). Multivariate survival analysis suggested that, along with other parameters, ADAM17 and EMMPRIN expression were independent prognostic factors for patients with gastric cancer. ADAM17 was implicated in the progression of gastric cancer. On the basis of the TNM stage, detection of ADAM17 expression will be helpful for predicting prognosis of gastric cancer.