【作者】 龚辉成；

【导师】 于锋；

【作者基本信息】 广州医学院 ， 耳鼻咽喉头颈外科， 2009， 硕士

【摘要】 目的:鼻咽癌是一种上皮源性恶性肿瘤,绝大多数属于低分化鳞状细胞癌,恶性程度高,早期易发生淋巴结和全身远处转移,具有相当高的死亡率。鼻咽癌的发病机制尚未明确。本研究旨在根据本科室已有鼻咽癌基因表达谱芯片结果,寻找鼻咽癌组织与正常粘膜组织间的异常表达基因,利用生物信息学方法筛选参与鼻咽癌的信号转导相关基因,并采用相关分子生物学实验初步验证筛选出鼻咽癌信号转导相关基因在鼻咽癌组织中的表达情况。方法:本研究采用本科室已有深圳微芯公司基于玻片的包含8046个人类基因的基因芯片结果,初步获得鼻咽癌异常表达基因;进而结合GO分类从基因芯片异常表达的基因中筛选信号转导相关基因;以Biocarta信号通路数据库查询筛选基因相关转导信号通路信息,结合文献进一步分析在鼻咽癌发生发展过程中信号转导相关基因相关信息。进而进一步利用分子生物学实验real-time q-PCR验证筛选出鼻咽癌信号转导相关基因在鼻咽癌组织与鼻咽炎组织中的表达情况。结果:1.以鼻咽癌基因芯片结果为基础,在鼻咽癌组织获得1214个异常用表达基因,其中高表达的基因有871个;在鼻咽癌组织低表达的基因343个。2.发现鼻咽癌差异表达基因中共有28个差异表达基因与细胞的信号转导相关,其中表达上调的21个,表达下调的7个,它们是:NRG2、SCYA3、PDGFA、SCYA18、SCYB10、SCYA4、INHBA、SCYA2、SCYA13、EFNA1、SFRP1、IL1A、HDGF、DKK1、TNFSF7、ECGF1、TNFSF4、NRTN、GRN、S100A9、MIF、IGFBP5、GRO1、SDF1、IGF2、C3、PTN、SEL1L。3.从单个基因的信号通路的角度,我们得到了7个信号转导相关基因的相应信号转导通路信息,它们可能在鼻咽癌的发生发展中起重要作用。4.通过应用实时荧光定量PCR(real-time quantitative PCR)技术对PDGFA和MIF两个基因在鼻咽癌组织中的表达进行检测,我们发现PDGFA和MIF两个基因在鼻咽癌组织中的表达比鼻咽炎组织高,这与基因芯片结果一致。结论:1.建立一种利用具有组织特异性鼻咽癌基因表达谱,进一步并利用生物信息学方法筛选鼻咽癌中信号转导相关基因的方法。2.鼻咽癌异常表达的信号转导相关基因介导通路在鼻咽癌的发生、发展中可能具有重要意义,PDGFA和MIF两个基因在鼻咽癌组织中表达异常得以明确。为阐明鼻咽癌的发病机制,鼻咽癌早期诊断、基因治疗及预后的进一步研究提供依据与参考。更多还原

【Abstract】 Objective:Nasopharyngeal carcinoma(NPC) is one of epithele origin malignant tumor, most of them are poorly differentiated squamous-cell carcinoma, and the cancer cell will reach the lymphadens of all over the body, and the death rate is very high.While the pathogenesy of NPC is unclear now. This study was to screen signal transduction -regulated genes from gene chips in NPC and then make a preliminary identification of the Candidate Gene.Methods:A preliminary selection of abnormal expression genes from the gene chips of the Shenzhen Weixin company which detected the seven nasopharyngeal carcinoma and one rhinopharyngitis. And then to integrate the data of signal transduction -regulated by Gene Ontology, screen signal transduction -regulated genes from gene chips in NPC from BioCarta,make a preliminary identification of the Candidate Gene by real-time quantitative PCR..Result:1.In the basic of gene chips, there are 871 high expression genes and 343 low expression genes in the nasopharyngeal carcinoma tissue.2.There are 27 differential expression relate gene of signal conducting.21 of them are high expressing and 7 are low express.They are NRG2、SCYA3、PDGFA、SCYA18、SCYB10、SCYA4、INHBA、SCYA2、SCYA13、EFNA1、SFRP1、IL1A、HDGF、DKK1、TNFSF7、ECGF1、TNFSF4、NRTN、GRN、S100A9、MIF、IGFBP5、GRO1、SDF1、IGF2、C3、PTN、SEL1L。 3.We accepted 7 signal transduction -regulated genes from BioCarta which could play important role in the development of NPC. And we got several signal pathways.4.We found that the two gene PDGFA and MIF high expressed in NPC,and that was according to the gene chips.Conclusion:1.We found a new way how to screen signal transduction-regulated genes from gene chips in NPC and then make a preliminary identification of the Candidate Gene.2.The differential expression relate gene PDGFA and MIF play an important role in the nasopharyngeal carcinoma’s emerging. And our study can be helpful in the pathogenetic and the gene therapy of nasopharyngeal carcinoma.更多还原