J Cancer 2016; 7(12):1716-1723. doi:10.7150/jca.15667
Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma
1. Department of Pathology, Chi-Mei Medical Center, Liouying, Taiwan;
2. Departments of Colorectal Surgery, Yuan's General Hospital, Kaohsiung, Taiwan;
3. Department of Health Business Administration, Meiho University, Pingtung, Taiwan;
4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan;
5. Division of General Surgery, Chi Mei Medical Center, Tainan, Taiwan;
6. Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, Taiwan;
7. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan;
8. Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;
9. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
10. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;
11. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
12. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
13. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
14. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lee YY, Chao TB, Sheu MJ, Tian YF, Chen TJ, Lee SW, He HL, Chang IW, Hsing CH, Lin CY, Li CF. Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma. J Cancer 2016; 7(12):1716-1723. doi:10.7150/jca.15667. Available from http://www.jcancer.org/v07p1716.htm
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, nasopharyngeal carcinoma, glutamate acid decarboxylase 1, γ-aminobutyric acid, transcriptome, Prognosis.