NEDD9 overexpression correlates with poor prognosis in gastric cancer

Abstract

In this study, the expression of neural precursor cell expressed developmentally downregulated 9 (NEDD9) in benign and malignant gastric tissues was investigated, and the significance of NEDD9 in gastric cancer prognosis was explored. Immunohistochemistry was used to detect NEDD9 expression in gastric cancer, nontumor gastric, and normal gastric tissues. The relationship between NEDD9 expression in gastric cancer tissues and the clinicopathologic factors was examined using the Mann-Whitney U test. The two factors between NEDD9 expression and tumor node metastasis (TNM) stage in gastric cancer patients were analyzed by Spearman rank correlation analysis. The Kaplan-Meier method and log-rank test were used to compare the overall survival of NEDD9 negative, weak positive expression, and strong positive expression group. NEDD9 expression rates were significantly higher (P < 0.001) in gastric cancer tissues (162 out of 187, 86.6 %) compared with normal (2 out of 11, 18.2 %) and nontumor (11 out of 58, 19.0 %) gastric tissues. The upregulated NEDD9 expression in gastric cancer tissue was significantly correlated with high preoperative CEA level (P = 0.044), poor differentiation (P = 0.007), tissue invasion (P = 0.015), present lymph node metastasis (P < 0.001), and high TNM stage (P < 0.001). NEDD9 expression was positively correlated with clinical TNM stage. Advancing clinical TNM stage corresponded with higher NEDD9 expression (r s = 0.289, P < 0.001). The overall 5-year survival of gastric cancer patients with strong positive NEDD9 expression was significantly shorter compared with the survival of NEDD9 negative and weakly positive expression group. NEDD9 may be used as a biomarker in the clinical setting to predict the prognosis of gastric cancer patients.

Elevated expression of NEDD9 is associated with&nbsp;metastatic activity in gastric cancer

“…Their results showed that the expression of NEDD9 was upregulated in GC, and that high expression of Nedd9 significantly correlated with cancer progression and poor prognosis in GC. 9 , 33 These results suggest an important role of NEDD9 in the progression of GC.…”

Nedd4-1 is an exceptional prognostic biomarker for gastric cardia adenocarcinoma and functionally associated with metastasis

“…These substrates include receptor or non-receptor tyrosine kinases, serine/threonine kinases and other signaling molecules [ 14 – 20 ]. In addition, very recent studies found that the Crk-associated focal adhesion protein Nedd9 is overexpressed in gastric cancer and tightly associated with metastasis [ 8 – 10 ]. The functional resemblance of Nedd9 to Nedd4-1 in gastric cancer metastasis may be yielded from a connected biochemical process.…”

“…There are a few molecular biomarkers of GCA, such as Sirt1, ErbB2, MCM2, identified in recent years [ 5 – 7 ]. Very recently, Nedd9, a Crk-associated protein involved in focal adhesion, has been found overexpressed in gastric cancer [ 8 – 10 ]. Expression of Nedd9 is tightly associated with gastric cancer progression, particularly metastasis.…”

Roles of neural precursor cell expressed, developmentally downregulated 9 in tumor-associated cellular processes (Review)

“…Previous studies of NEDD9 focused on the first step of cell invasion: Tumor cells escaping from the settlement site (65,66). Therefore, it is likely that activation of NEDD9 may lead to cell migration.…”