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 identifiedGAD1as 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.
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Liouying, Taiwan.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Departments of Colorectal Surgery, Yuan's General Hospital, Kaohsiung, Taiwan;; Department of Health Business Administration, Meiho University, Pingtung, Taiwan.
authors.forename: Tung-Bo
authors.initials: TB
authors.lastname: Chao
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.affiliation: Division of General Surgery, Chi Mei Medical Center, Tainan, Taiwan;; Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Tian
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Tzu-Ju
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: He
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan;; Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Ching-Yih
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan;; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;; Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
keywords: GAD1; Prognosis.; glutamate acid decarboxylase 1; nasopharyngeal carcinoma; transcriptome; γ-aminobutyric acid