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Title: | Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma |
Authors: | Lee, YY;Chao, TB;Sheu, MJ;Tian, YF;Chen, TJ;Lee, SW;He, HL;Chang, IW;Hsing, CH;Lin, CY;Li, CF |
Contributors: | National Institute of Cancer Research |
Abstract: | Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of gamma-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities. |
Date: | 2016-07-27 |
Relation: | Journal of Cancer. 2016 Jul 27;7(12):1716-1723. |
Link to: | http://dx.doi.org/10.7150/jca.15667 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1837-9664&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000393076400016 |
Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85008496951 |
Appears in Collections: | [其他] 期刊論文
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