福建肝癌高发家系染色体亚畸变及基因差异表达聚类分析

发布时间：2018-03-03 04:26

本文选题：肝癌高发家系　切入点：一级亲属　出处：《福建医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:筛查福建肝癌高发家系肝癌患者、患者一级亲属与正常对照组的亚畸变染色体及差异基因,并通过聚类分析定位基因产物功能。方法:采血抽提肝癌高发家系肝癌组、患者一级亲属组、健康对照组基因组,采用高分辨率微阵列比较基因杂交技术(array-CGH)进行全基因组扫描,筛查出亚畸变染色体及差异基因,应用GORILLA在线分析软件对差异基因进行聚类分析。结果:染色体亚畸变及基因差异:肝癌组、亲属组、对照组均有不同程度的DNA拷贝数差异(扩增和缺失),共检查出亚畸变染色体区段86处,涉及206个差异基因。各组间染色体平均扩增数及缺失数差异无统计学意义(P=0.945)。染色体扩增和缺失频率在三组间的差异均无统计学意义(P0.05)。差异基因频率在三组间的差异均无统计学意义(P0.05)。聚类分析结果:206个差异基因进行聚类分析后,其中31个基因存在显著富集,分别为APOBEC3A、APOBEC3B、DEFB103A、DEFB103B、DEFB104A、DEFB104B、DEFB105A、DEFB105B、DEFB106A、DEFB106B、DEFB107A、DEFB107B、NPY4R、OR11H12、OR11H2、OR2T10、OR2T11、OR2T34、OR2T35、OR4C6、OR4K1、OR4K2、OR4K5、OR4M1、OR4M2、OR4N2、OR4N4、OR4P4、OR4Q3、OR4S2、ZDHHC11。上述差异基因主要存在于细胞膜部分;分子功能上表现为G蛋白偶联受体活性、跨膜受体活性、信号转导、嗅觉受体活性、分子转导活性;在生物学过程中与G蛋白偶联受体信号通路、对化学刺激的感知、对刺激的感知、信号转导、嗅觉感知、调控细胞过程、调节生物进程等相关。其中GO:0004930(P=1.43E-10)和GO:0007186(P=3.95E-10)富集最为显著。结论:(1)肝癌患者存在明显的染色体扩增和缺失,且部分染色体亚畸变是非随机的(频率超过10%被认为是非随机位点);(2)本研究中染色体亚畸变及差异基因与福建肝癌高发家系肝癌的发生无显著相关性;(3)G蛋白偶联受体及其介导的信号通路可能与福建原发性肝癌的发生、发展有关。
[Abstract]:Objective: to screen subaberrant chromosomes and differentially expressed genes between first-degree relatives and normal controls in a family with high incidence of liver cancer in Fujian Province, and to locate the function of gene products by cluster analysis. The first degree relatives of the patients and the healthy control group were scanned by high-resolution microarray comparative gene hybridization technique to screen subaberrant chromosomes and differential genes. GORILLA online analysis software was used to cluster analysis of differential genes. Results: chromosome subaberration and gene difference: liver cancer group, relatives group, In the control group, there were different DNA copy numbers to varying degrees (amplification and deletion), and 86 subaberration chromosomal regions were detected. There was no significant difference in the average number of chromosomes and the number of deletions among the three groups. There was no significant difference in the frequency of chromosome amplification and deletion among the three groups, and there was no significant difference in the frequency of chromosome amplification and deletion among the three groups. The difference in the frequency of the differentially expressed genes among the three groups was not significant. The results of cluster analysis showed that 206 differentially expressed genes were analyzed by cluster analysis. Among them, 31 genes were significantly enriched, namely APOBEC3B3DEFB103AB103A, DEFB104ADEFB104ADEFB105ADEFB105ADEFB105ADEFB105ADEFB105ADEFB106ADEFB106ADEFB107BNPY107BNPY4ROR11H12H2OR2T10OR2T10OR2T32OR2T3OR2T3OR4C6OR4K4K2OR4K1OR4M1O4N4N4N4OR4OR4OR4OR4OR4OR4Q4S2H2H2OR2OR2OR2T2T3OR2OR2OB104OR4K2OR4M4N4N4N4N4OR4OR4OR4OR4Q4S2OB107BB107BNPY4ROR11H12H2OR2T102OR2T2OR2T3OR2T3OR2OR4C6O4K4K2OR4M4M2N4N4N4OR4OR4OR4OR4OR4OR4OQ4OQ4OQ4OQ2OQ2H2OR2OR2T2OB102OR2T2OR2T3OR2T3OR2OR2T102T3OR2OR2T3OR2OR2@@. Molecular transduction activity; receptor signaling pathway coupled with G protein in biological processes, perception of chemical stimuli, perception of stimuli, signal transduction, olfactory perception, regulation of cellular processes, Regulation of biological processes, among them, the enrichment of GO0004930 (1.43E-10) and GO00071866 (Pn3.95E-10) is the most significant. Conclusion there is significant chromosome amplification and deletion in patients with liver cancer. And some chromosomal subaberrations are non-random (frequency over 10% is considered as non-random locus) in this study, there is no significant correlation between chromosomal subaberration and differential genes and the occurrence of HCC in Fujian high incidence families. Receptor and its mediated signaling pathway may be associated with the occurrence of primary liver cancer in Fujian. Development is relevant.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.7

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