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Molecular Cancer

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Open Access 01-12-2014 | Research

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

Authors: Aiqin Sun, Guanzhen Yu, Xiaoyan Dou, Xiaowei Yan, Wannian Yang, Qiong Lin

Published in: Molecular Cancer | Issue 1/2014

Abstract

Background

Gastric cardia adenocarcinoma (GCA) is the most aggressive subtype of gastric carcinoma. New molecular markers and therapeutic targets are needed for diagnosis, prognosis and treatment of GCA. This study is to establish the E3 ubiquitin ligase Nedd4-1 as a prognostic biomarker to predict the survival and guide the treatment of GCA patients.

Methods

Expression of Nedd4-1 in 214 GCA tumor samples was detected by immunohistochemistry staining (IHC) using tissue microarray assay (TMA). Association of Nedd4-1 with cumulative survival of the TNM stages I-III patients and clinicopathological characteristics was statistically analyzed. The role of Nedd4-1 in gastric cancer cell migration and invasion were determined by transwell and wound healing assays.

Results

Nedd4-1 is overexpressed in 83% of the GCA tumors. The 5-year survival rate in Nedd4-1 negative GCA patients is as high as 96%. Log-rank analysis indicated that overexpression of Nedd4-1 is inversely correlated with cumulative survival (χ² = 21.885, p <0.001). Multivariate logistic regression analysis showed that overexpression of Nedd4-1 is associated with an extremely low GCA survival rate with a hazard ratio (HR) = 0.068 (p = 0.008) in TNM stages I-III patients. Statistical analysis of association of Nedd4-1 overexpression with clinicopathological characteristics revealed that overexpression of Nedd4-1 is tightly associated with TNM stage (p < 0.001). Knockdown of Nedd4-1 in gastric cancer cell lines AGS and N87 dramatically inhibited the gastric cancer cell migration and invasion.

Conclusions

Our results indicate that Nedd4-1 is an exceptional prognostic biomarker for GCA and suggest that Nedd4-1 may play an essential role in GCA metastasis.

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Title: Nedd4-1 is an exceptional prognostic biomarker for gastric cardia adenocarcinoma and functionally associated with metastasis
Authors: Aiqin Sun
Guanzhen Yu
Xiaoyan Dou
Xiaowei Yan
Wannian Yang
Qiong Lin
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-13-248

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