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.
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References
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.
Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.
Law SF, Estojak J, Wang B, et al. Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16(7):3327–37.
Minegishi M, Tachibana K, Sato T, et al. Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes. J Exp Med. 1996;184(4):1365–75.
Kumar S, Tomooka Y, Noda M. Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun. 1992;185:1155–61.
Tikhmyanova N, Golemis EA. NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation. PLoS One. 2011;6:e22102.
Kim M, Gans JD, Nogueira C, et al. Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell. 2006;125(7):1269–81.
Natarajan M, Stewart JE, Golemis EA, et al. HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene. 2006;25(12):1721–32.
Guo W, Ren D, Chen X, et al. HEF1 promotes epithelial mesenchymal transition and bone invasion in prostate cancer under the regulation of microRNA-145. J Cell Biochem. 2013;114(7):1606–15.
Xue YZ, Sheng YY, Liu ZL, et al. Expression of NEDD9 in pancreatic ductal adenocarcinoma and its clinical significance. Tumour Biol. 2013;34(2):895–9.
Li Y, Bavarva JH, Wang Z, et al. HEF1, a novel target of Wnt signaling, promotes colonic cell migration and cancer progression. Oncogene. 2011;30:2633–43.
Xia D, Holla VR, Wang D, et al. HEF1 is a crucial mediator of the proliferative effects of prostaglandin E(2) on colon cancer cells. Cancer Res. 2010;70(2):824–31.
Kim SH, Xia D, Kim SW, et al. Human enhancer of filamentation 1 Is a mediator of hypoxia-inducible factor-1alpha-mediated migration in colorectal carcinoma cells. Cancer Res. 2010;70(10):4054–63.
Izumchenko E, Singh MK, Plotnikova OV, et al. NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res. 2009;69:7198–206.
Sima N, Cheng X, Ye F, et al. The overexpression of scaffolding protein NEDD9 promotes migration and invasion in cervical cancer via tyrosine phosphorylated FAK and SRC. PLoS One. 2013;8(9):e74594.
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This study was supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (JX10231801) and grants from Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments.”
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Yi Liu, Ding Wang, and Kui-ling Zhao are co-first authors.
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Liu, Y., Wang, D., Zhao, KL. et al. NEDD9 overexpression correlates with poor prognosis in gastric cancer. Tumor Biol. 35, 6351–6356 (2014). https://doi.org/10.1007/s13277-014-1839-7
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DOI: https://doi.org/10.1007/s13277-014-1839-7