γ-氨基丁酸受体在非小细胞肺癌中的基因表型及其预后的指导意义

The gene phenotype of gamma-aminobutyric acid receptor and its prognostic significance in non- small cell lung cancer

目的：探讨非小细胞肺癌（NSCLC）组织中γ-氨基丁酸受体（GABAR）表型与肿瘤的发生发展及临床预后的相关性。方法收集中国南方人肺癌标本库中2007年1月1日至2012年10月31日的NSCLC组织及癌旁正常肺组织（癌旁5 cm）标本61例，采用定量PCR方法对其GABAR基因表达进行差异检测，分析患者的性别、年龄、吸烟史、组织学类型、TNM分期以及其他GABAR亚型的表达高低与5年生存率的关系。结果在NSCLC组织中，GABAA受体亚型α3、ε和GABAB受体亚型2的基因表达较癌旁正常组织明显增高（均P〈0.05）。高表达GABBR2和低表达GABRA3的患者具有较好的生存预后（均P〈0.05），生存率分别为62%和76%；吸烟和TNM分期也是影响预后的重要因素（均P〈0.05）；性别、年龄、组织学类型以及其他GABAR亚型的表达高低对预后无影响。结论 GABAR的基因表型与肿瘤的发生发展密切相关，这些特定的受体基因有望成为NSCLC新的分子治疗靶点和预测预后因子。

Objective To investigate the correlation between the phenotype of γ-aminobutyric acid receptor（GABAR）and the occurrence,development and clinical prognosis in non-small cell lung cancer （NSCLC）. Methods Sixty-one paired samples of NSCLC tissues and normal lung tissues（5cm adjacent to carcinoma） collected from Chinese Southern Lung Cancer Tissue Bank between January 1st,2007 and October 31st,2012 were included in the study. The differential expression of GABAR gene was determined by quantitative PCR. The gender,age,smoking history,histological type,tumor node metastasis （TNM） classification,and the expressions of other GABAR subtypes were analyzed for any correlation with the 5-year survival in the patients. Results The gene expressions of GABAA receptor subtypes α3,ε,and GABAB receptor subtype 2 in NSCLC tissues were significantly increased compared with those in normal lung tissues adjacent to carcinoma （all P〈0.05）. Patients with high expression of GABBR2 gene and low＆amp;nbsp;expression of GABRA3 gene had better prognosis（all P〈0.05）,with the survival rate being 62%and 76%, respectively. The smoking history and TNM classification were important influential factors for prognosis（all P〈0.05）,whereas gender,age,histological type,and the high/low expression of other GABAR subtypes had no influences on the prognosis. Conclusion The gene phenotype of GABAR is closely correlated with the occurrence and development of NSCLC. These specific receptor genes may become new molecular therapeutic targets and prognostic predictors for NSCLC.