Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma

Yi Ying Lee, Tung Bo Chao, Ming Jen Sheu, Yu Feng Tian, Tzu Ju Chen, Sung Wei Lee, Hong Lin He, I. Wei Chang, Chung Hsi Hsing, Ching Yih Lin, Chien Feng Li

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4 Citations (Scopus)

Abstract

Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-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.

Original languageEnglish
Pages (from-to)1716-1723
Number of pages8
JournalJournal of Cancer
Volume7
Issue number12
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • GAD1
  • Glutamate acid decarboxylase 1
  • Nasopharyngeal carcinoma
  • Prognosis
  • Transcriptome
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Lee, Y. Y., Chao, T. B., Sheu, M. J., Tian, Y. F., Chen, T. J., Lee, S. W., He, H. L., Chang, I. W., Hsing, C. H., Lin, C. Y., & Li, C. F. (2016). Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Journal of Cancer, 7(12), 1716-1723. https://doi.org/10.7150/jca.15667