碱基切除修复基因在人鼻咽癌组织和鼻咽非癌组织中的表达及其意义

Expression and Implication of Base Excision Repair Genes in Human Nasopharyngeal Carcinoma and Non-tumor Nasopharyngeal Tissues

背景与目的:碱基切除修复基因对于维护基因组稳定性具有重要的作用,其表达异常与多种肿瘤相关。本实验研究7个重要的碱基切除修复基因(hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3)在鼻咽癌及鼻咽非癌组织中的表达及其意义。方法:用RT-PCR方法分析24例鼻咽癌组织和24例鼻咽非癌组织中hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3基因的表达。对有表达差异的基因hOGG1和ADPRT进一步用免疫组化的方法在99例鼻咽癌组织和28例鼻咽非癌组织中进行验证。结果:RT-PCR结果表明hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3基因在鼻咽癌和鼻咽非癌组织中均表达。其中,hOGG1和ADPRT在鼻咽癌组织中的mRNA水平显著低于鼻咽非癌组织(P<0.001)。免疫组化验证了两基因的蛋白水平在鼻咽癌组织中降低。在鼻咽癌组织和鼻咽非癌组织中,hOGG1基因高表达率分别50.5%和92.8%(P<0.001),而ADPRT基因分别是53.5%和96.4%(P<0.001)。但两基因的表达水平与鼻咽癌的临床分期和预后无关。结论:hOGG1和ADPRT基因的表达降低,可能与鼻咽癌的发生发展密切相关。

BACKGROUND ＆ OBJECTIVE： Base excision repair （BER） genes play important roles in maintaining genomic stability and their abnormal expression are associated with several cancers. This study was to investigate the expression of 7 important BER genes （hOGG1, ADPRT, APE1, MBD4, POLB, XRCC1 and LIG3） in nasopharyngeal carcinoma （NPC） and non-tumor nasopharyngeal tissues, and evaluate their clinical significance. METHODS： The expression of hOGG1, ADPRT, APE1, MBD4, POLB, XRCC1 and LIG3 in 24 specimens of NPC and 24 specimens of non-tumor nasopharyngeal tissues was detected by reverse transcription-polymerase chain reaction （RT-PCR）. The differential expression of hOGG1 and ADPRT was further detected by immunohistochemistry in 99 specimens of NPC and 28 specimens of non-tumor nasopharyngeal tissues. RESULTS： hOGG1, ADPRT, APE1, MBD4, POLB, XRCC1 and LIG3 were expressed in both NPC and non-tumor nasopharyngeal tissues. Among them, the mRNA levels of hOGG1 and ADPRT were significantly lower in NPC than in non-tumor nasopharyngeal tissues （P〈0.001）. The protein levels of hOGG1 and ADPRT in NPC were also reduced. The high expression rates of hOGG1 were 50.5% in NPC and and 92.8% in non-tumor nasopharyngeal tissues （P〈0.001）, and those of ADPRT were 53.5% and 96.4%, respectively （P〈0.001）. However, the expression levels of hOGG1 and ADPRT had no correlations to the clinical stage and prognosis of NPC. CONCLUSION： The decreased expression of hOGG1 and ADPRT might be closely related to the development of nasopharyngeal carcinoma.