基于表达谱芯片技术的食管鳞状细胞癌相关差异基因的筛选及功能研究

摘要

Obj ective]To screen the critical genes related to esophageal cancer by using chip data of the genes related to esophageal squamous cell cancer,and to investigate the function of the module of critical genes.[Methods]GSE1 7 3 5 1 data including 1 0 samples(5 normal samples and 5 esophageal squamous cell cancer samples)were down-loaded from gene expression GEO database.The R software package was used for data preprocessing and differential expression analysis.The differentially expressed genes were selected(FDR<0.05 or difference value>2 or <-2), and then analyzed by bioinformatics.Firstly,the protein-protein interaction network of the differentially expressed genes was obtained by String on-line-analysis tool(score>0.9),and the degree of each point in network was calculat-ed,and the critical hub gene was selected.Then Cytoscape software plugin Mcode was used for network modulariza-tion.Bingo plugin(P<0.05)was used for the functional note of module of hub gene.The mechanism and mode in-fluencing the differentially expressed genes causing esophageal cancer was inferred.[Results]Totally 600 differentially expressed genes were screened by comparing the expressed data of normal subj ects and patients with esophageal squa-mous cell cancer.The protein-protein interaction network which contained 2 6 8 pairs of proteins was constructed.The hub gene TOPA2 was found.The module including 5 differentially expressed genes containing hub gene was a-chieved.Module function was enriched in chromosome condensation and segregation. Chromosome active gene NCAPG interacting with hub gene TOPA2 related to multiple cancers was found.[Conclusion]The occurrence of e-sophageal squamous cell is related to the most important gene TOP2A.It infers that NCAPG gene interacting with TOP2A affects the expression of tumor specific genes through the same mechanism and mode of TOP2A(mid-pro-phase of chromosome).%目的利用食管鳞状细胞癌细胞相关基因芯片数据，筛选与食管癌显著相关的关键基因，并对关键基因所在的模块进行功能研究。方法从基因表达数据库 GEO 数据库中下载数据 GSE17351(数据共10个样本，正常和食管鳞状细胞癌样本组织各5个)，利用 R软件包做数据预处理和差异表达分析，选取差异表达基因(FDR <0.05及差异值>2或<-2)。然后对差异表达基因进行生物信息学分析，首先投入 String 在线分析工具获得差异表达基因的蛋白-蛋白相互作用网络(score>0.9)，统计网络中各个节点的度，挑选出最关键的主效基因(hub基因)。然后利用Cytoscape软件插件 Mcode对整个网络进行网络模块化，并通过插件Bingo(P value<0.05)对hub基因所在的模块进行功能注释，推测模块中影响基因特异性表达导致食管癌的机制和方式。结果通过比较正常和患病者食管鳞状细胞癌表达数据，筛选到600个差异表达的基因，构建了包含268对差异表达基因产物蛋白对的相互作用网络。找到最关键 hub 基因 TOP2A。得到1个包括hub基因在内由5个差异表达基因组成的模块，模块功能最显著富集在染色体分离和浓缩；发现与多种癌症相关的基因TOP2A共同起染色体活动基因 NCAPG。结论食管鳞癌的发生与最关键基因 TOP2A的异常表达有关，推测与之功能发生作用的基因 NCAPG 基因通过与 TOP2A 相同的机制和方式(染色体中前期活动)影响着癌症特异性基因的表达。