基于癌症基因组图谱筛查卵巢浆液性囊腺癌相关基因  

Gene microarray analysis of ovarian serous cystadenocarcinoma-related genes based on TCGA

作　　者：李典鹤[1] 黄昌男[1] 李奇[2] 

机构地区：[1]东北师范大学医院内科,吉林长春130024 [2]首都医科大学附属北京天坛医院临床医学研究实验室,北京100050

出　　处：《中国病理生理杂志》2016年第12期2276-2281,2286,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81303268);北京市自然科学基金资助项目(No.7152098)

摘　　要：目的:利用全基因组表达谱芯片筛查与卵巢浆液性囊腺癌发生相关的基因,对在卵巢浆液性囊腺癌发生过程中可能参与的基因间的信号转导通路进行分析。方法:选取癌症基因组图谱(TCGA)数据库中卵巢浆液性囊腺癌的Affymetrix Gene Chip Human Exon 1.0 ST Array数据共16张,分别为卵巢浆液性囊腺癌组8张和正常组8张,筛选出差异表达基因,并进行基因本体(gene ontology,GO)分析和信号通路分析,构建卵巢浆液性囊腺癌相关基因间的信号转导通路,分析网络中具有重要作用的基因。结果:共筛选出1 144个在卵巢癌中差异表达的基因,其中表达上调的基因有747个,表达下调的基因有397个。GO分析得到上调差异基因的显著性功能分析结果362项,下调差异基因的显著性功能分析结果 160项(P<0.05)。其中包括与肿瘤发生相关的基因功能有细胞周期、DNA复制、细胞增殖、细胞凋亡、细胞黏附等。信号通路分析得到45个显著上调信号通路和14个显著下调信号通路(P<0.05)。其中参与肿瘤发生相关的信号通路主要有细胞周期、P53信号通路、DNA复制、肿瘤中的信号通路、PI3K-Akt信号通路、ECM-receptor信号通路、细胞黏附因子、细胞凋亡等。挑选显著性基因功能和信号通路分析的交集基因229个,构建显著性GO与信号通路基因间信号转导网络。分析发现CDK1、PLK1、MCM3和PGK1这4个基因在卵巢癌的基因调控网络中具有重要作用。结论:卵巢浆液性囊腺癌中有大量差异表达基因,差异表达的基因在多个与肿瘤发生密切相关的信号通路中发挥重要的调控作用。AIM：To detect the differentially expressed genes associated with ovarian serous cystadenocarcinoma（ OV） by microarray and to analyze the participated signaling pathway.METHODS：We analyzed 16 datasets of Affymetrix Gene Chip Human Exon 1.0 ST Arrays from The Cancer Genome Atlas（ TCGA）,including 8 OV and 8 normal ovary samples.The function of differential genes was determined by pathway and gene ontology（ GO） analysis.The probable functions of the key genes were predicted according to intergenic signal transduction network.RESULTS：The 1 144 genes were identified as distinctively expressed in OV（ P〈0.05）,747 of which were up-regulated and 397 were down-regulated.The GO analysis results showed that the altered genes were involved in 362 up-regulated and 160 down-regulated significant functions（ P〈0.05） related to cell cycle,DNA replication,cell proliferation,cell apoptosis,cell adhesion,etc.The pathways of the different genes were involved in the 59 enrichment-related pathways（ P〈0.05）,45 of which were upregulated and 14 were down-regulated.Among the 59 pathways,cell cycle,P53 signaling pathway,DNA replication,pathways in cancer,PI3K-Akt signaling pathway,ECM-receptor signaling pathway,cell adhesion molecules and cell apoptosis were related to tumor genesis,development and metastasis.As a result,229 genes with significant functions and pathways in GO and pathway analysis were selected to construct signal transduction network（ Signal-Net）,4 of which,CDK1,PLK1,MCM3 and PGK1,were found to play key roles in OV signal regulation network.CONCLUSION：The OV shows abundant differentially expressed genes that play key roles in cancer-related signal pathways.

关 键 词：卵巢浆液性囊腺癌 基因芯片 差异表达 基因功能 信号通路 

分 类 号：R363[医药卫生—病理学]