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.
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.