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

Molecular Cancer

Research

Xiaowei Yan¹  Guanzhen Yu²  Xiaoyan Dou³  Aiqin Sun³  Qiong Lin⁴  Wannian Yang⁵ 

[1] Center for Health Research, 17822, Danville, PA, USA;Department of Oncology, Changzheng Hospital, Shanghai, China;School of Medical Sciences and Laboratory Medicine, Jiangsu University, 212013, Zhenjiang, China;School of Medical Sciences and Laboratory Medicine, Jiangsu University, 212013, Zhenjiang, China;Weis Center for Research, Geisinger Clinic, 17822, Danville, PA, USA;Weis Center for Research, Geisinger Clinic, 17822, Danville, PA, USA;

关键词: Gastric cardia adenocarcinoma;    Nedd4-1;    Prognostic biomarker;    Survival prediction;   

DOI  :  10.1186/1476-4598-13-248

 received in 2014-06-10, accepted in 2014-10-29,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundGastric 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.MethodsExpression 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.ResultsNedd4-1 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Sun et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.