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

Research output: Contribution to journalArticle

2 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

Fingerprint

Survival
Neoplasm Metastasis
Recurrence
Survival Rate
Aminobutyrates
glutamate decarboxylase 1
Nasopharyngeal carcinoma
GABAergic Neurons
Neoplasms
Data Mining
Transcriptome
gamma-Aminobutyric Acid
Therapeutics
Central Nervous System
Immunohistochemistry
Databases
Biopsy
Enzymes
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Lee, Y. Y., Chao, T. B., Sheu, M. J., Tian, Y. F., Chen, T. J., Lee, S. W., ... 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

Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. / Lee, Yi Ying; Chao, Tung Bo; Sheu, Ming Jen; Tian, Yu Feng; Chen, Tzu Ju; Lee, Sung Wei; He, Hong Lin; Chang, I. Wei; Hsing, Chung Hsi; Lin, Ching Yih; Li, Chien Feng.

In: Journal of Cancer, Vol. 7, No. 12, 2016, p. 1716-1723.

Research output: Contribution to journalArticle

Lee, YY, Chao, TB, Sheu, MJ, Tian, YF, Chen, TJ, Lee, SW, He, HL, Chang, IW, Hsing, CH, Lin, CY & Li, CF 2016, 'Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma', Journal of Cancer, vol. 7, no. 12, pp. 1716-1723. https://doi.org/10.7150/jca.15667
Lee, Yi Ying ; Chao, Tung Bo ; Sheu, Ming Jen ; Tian, Yu Feng ; Chen, Tzu Ju ; Lee, Sung Wei ; He, Hong Lin ; Chang, I. Wei ; Hsing, Chung Hsi ; Lin, Ching Yih ; Li, Chien Feng. / Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. In: Journal of Cancer. 2016 ; Vol. 7, No. 12. pp. 1716-1723.
@article{dad2f9b16e844c12bb79ab518943d461,
title = "Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma",
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.",
keywords = "GAD1, Glutamate acid decarboxylase 1, Nasopharyngeal carcinoma, Prognosis, Transcriptome, γ-aminobutyric acid",
author = "Lee, {Yi Ying} and Chao, {Tung Bo} and Sheu, {Ming Jen} and Tian, {Yu Feng} and Chen, {Tzu Ju} and Lee, {Sung Wei} and He, {Hong Lin} and Chang, {I. Wei} and Hsing, {Chung Hsi} and Lin, {Ching Yih} and Li, {Chien Feng}",
year = "2016",
doi = "10.7150/jca.15667",
language = "English",
volume = "7",
pages = "1716--1723",
journal = "Journal of Cancer",
issn = "1837-9664",
publisher = "Ivyspring International Publisher",
number = "12",

}

TY - JOUR

T1 - Glutamate decarboxylase 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma

AU - Lee, Yi Ying

AU - Chao, Tung Bo

AU - Sheu, Ming Jen

AU - Tian, Yu Feng

AU - Chen, Tzu Ju

AU - Lee, Sung Wei

AU - He, Hong Lin

AU - Chang, I. Wei

AU - Hsing, Chung Hsi

AU - Lin, Ching Yih

AU - Li, Chien Feng

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - GAD1

KW - Glutamate acid decarboxylase 1

KW - Nasopharyngeal carcinoma

KW - Prognosis

KW - Transcriptome

KW - γ-aminobutyric acid

UR - http://www.scopus.com/inward/record.url?scp=85008496951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008496951&partnerID=8YFLogxK

U2 - 10.7150/jca.15667

DO - 10.7150/jca.15667

M3 - Article

VL - 7

SP - 1716

EP - 1723

JO - Journal of Cancer

JF - Journal of Cancer

SN - 1837-9664

IS - 12

ER -