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
Department of Pathology, Chi-Mei Medical Center, Liouying, Taiwan.
Departments of Colorectal Surgery, Yuan's General Hospital, Kaohsiung, Taiwan;; Department of Health Business Administration, Meiho University, Pingtung, Taiwan.
J Cancer. 2016 Jul 27;7(12):1716-1723. doi: 10.7150/jca.15667. eCollection 2016.
: 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 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. : 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. : GAD1 overexpression was significantly associated with an increase in the primary tumor status ( < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV ( = 0.002) and was a univariate predictor of adverse outcomes of DSS ( = 0.002), DMeFS ( < 0.0001), and LRFS ( = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS ( = 0.004, hazard ratio = 2.234), DMeFS ( < 0.001, hazard ratio = 4.218), and LRFS ( = 0.013, hazard ratio = 2.441) rates. : 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.
谷氨酸脱羧酶1（GAD1）作为参与γ-氨基丁酸（GABA）生成的限速酶，存在于中枢神经系统（CNS）的GABA能神经元中。关于GAD1与鼻咽癌（NPC）的相关性知之甚少。通过对一个来自已发表转录组数据库的数据集进行数据挖掘，本研究首次将其鉴定为NPC中差异上调的基因。我们旨在评估GAD1的表达及其对早期和局部晚期NPC患者的预后影响。：我们评估了124例接受治疗的非转移性NPC患者活检标本的GAD1免疫组化并进行了H评分分析。GAD1过表达定义为H评分高于中位数。该分析结果与临床病理行为和生存率相关，即疾病特异性生存率（DSS）、无远处转移生存率（DMeFS）和无局部复发生存率（LRFS）。：GAD1过表达与原发肿瘤状态增加（<0.001）和美国癌症联合委员会（AJCC）III-IV期（=0.002）显著相关，并且是DSS（=0.002）、DMeFS（<0.0001）和LRFS（=0.001）不良结局的单因素预测指标。在多因素比较中，除了AJCC III-IV期晚期外,GAD1过表达仍然是DSS缩短（=0.004，风险比=2.234）、DMeFS（<0.001，风险比=4.218）和LRFS（=0.013，风险比=2.441）率的独立预后指标。：我们的数据显示，GAD1过表达与疾病进展状态相关，因此可能是NPC不良结局的关键预后指标和促进有效治疗模式发展的潜在治疗靶点。
