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鼻咽癌分子标志物研究

Biomarkers of Nasopharyngeal Carcinoma

【作者】 张文玲周艳宏肖岚范松青曾朝阳李小玲武明花李桂源

【Author】 ZHANG Wen-Ling1),ZHOU Yan-Hong1),XIAO Lan1),FAN Song-Qing2), ZENG Zhao-Yang1),LI Xiao-Ling1),WU Ming-Hua1),LI Gui-Yuan1)(1) Cancer Research Institute,Central South University,Changsha 410078,China; 2) Department of Pathology,The Second Xiangya Hospital of Central South University,Changsha 410011,China)

【机构】 中南大学肿瘤研究所中南大学湘雅二医院病理科中南大学肿瘤研究所 长沙410078长沙410078长沙410011

【摘要】 鼻咽癌严重危害人类健康,寻找其早期诊断及预后相关的分子标志物迫在眉睫.在总结本课题组运用基因组学、转录组学、蛋白质组学和组织微阵列等高通量技术对不同分化阶段、不同组织类型和不同临床分期的鼻咽癌标本进行大规模筛选工作的基础上,结合近年国际上有关进展,初步构建了鼻咽癌不同发病阶段的分子靶标系统:a.证实SPLUNC1、p16、EBER-1、p27、RASSF1A和CDH13是鼻咽癌早期诊断的理想分子靶标;b.鼻咽癌上调基因RB1,STMN1和DSP及下调基因SERPINB6,AGTRL1和SYTL2的分类预测模型是区分正常鼻咽上皮和鼻咽癌的分子靶标;c.NGX6、Ezrin、LTF、OPN、THY1和Tiam-1是鼻咽癌侵袭与转移预测的候选分子靶标;d.Cyclin D1、Survivin和HPA是与鼻咽癌预后相关的候选分子标志物;e.证实Bcl-2、EGFR和Ki67是预测鼻咽癌放疗敏感与否的候选分子靶标;f.SAA和cox-2是监测鼻咽癌复发的候选分子标志物;g.发现BRD7、NGX6、NOR1和UBAP1的6个SNP改变是鼻咽癌遗传易感风险因子;h.建立了由139个基因组成的鼻咽癌不同临床分期分子靶标系统.这些在大样本基础上的分子靶标筛选为鼻咽癌分子分型研究奠定了重要工作基础.

【Abstract】 Nasopharyngeal carcinoma(NPC) is a malignant disease which had critically threatened human’s health.It is very important to look for the biomarkers related to early diagnosis and prognosis of NPC.Using a series of large scale screening techniques from genomics,transcriptomics,proteomics and tissue microarray,combined with some international progress,a molecular marker system had been preliminarily constructed in different stages of NPC:(1) SPLUNC1,EBER-1,p16,p27,RASSF1A and CDH13,a group of molecular targets for the early diagnosis of NPC.(2) The class forecast model consisting of up-regulated RB1,STMN1,DSP and down-regulating SERPINB6,AGTRL1,SYTL2,the biomarkers to identify between normal nasopharyngeal epithelium and NPC.(3) NGX6,Ezrin,LTF,OPN,THY1 and Tiam-1,a group of candidate biomarkers forcasting the invasion and metastasis of NPC.(4) Cyclin D1,Survivin and HPA,a group of biomarkers related to the prognosis of NPC.(5) Bcl-2、EGFR and Ki67 proteins,a group of perfect candidate biomarkers for forecasting radiation sensitivity of NPC.(6) SAA and cox-2,the candidate biomarkers monitoring NPC recurrence.(7) The changes of six SNP from BRD7,NGX6,NOR1 and UBAP1,a group of the inheritance susceptibility risk factors.(8) Constructing a biomarker system of different clinical stages of NPC composed of 139 genes.These biomarkers based on screening with large amounts of samples lay an important foundation for molecular typing research of NPC.

【关键词】 鼻咽癌; 癌基因; 抑癌基因; 分子靶标;

【Key words】 nasopharyngeal carcinoma; oncogene; tumor suppressor gene; molecular markers;

【分类号】R739.63;R394.21;R449;

【基金】 国家重点基础研究发展计划(973)(2006CB910502,2006CB910504);国家自然科学基金(30770825,30700469);国家高技术研究发展计划(863)(2007AA02Z170);全国优秀博士学位论文作者专项基金(200559)资助项目.~~

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