用生物信息学方法筛选人类和大鼠共同肝癌相关基因

Using bioinformatics to screen common key genes in hepatocellular carcinoma in human and rat

目的应用生物信息学技术，对基因芯片产生的大量数据进行系统地挖掘和分析，筛选在人类和大鼠不同种属间肝癌发生发展过程中起关键作用的共同基因。方法首先通过文献检索，在GEO数据库中下载符合纳入标准的3套样本基因芯片数据。运用bioconductor和Rversion的2．10．1版本对已下载数据进行标准化处理，运用软件包affy中的RMA算法对affymetrix平台的原始数据进行背景校正、标准化和log2转换；然后用excel的TTEST函数计算每一个基因的显著性，用DAVID进行探针基因名称转换，建立基因名称与样本对应的表达数据表；最后再进行Meta分析计算人类及大鼠的共同差显基因，并通过DAVID中的KEGG库富集调控通路。结果共检出人类与大鼠肝癌发生发展过程中的共同表达基因26个，其中5个为上调基因，21个为下调基因；富集出1条通路，即黏附斑通路，已有文献报道其与肝癌的发生发展密切相关。结论采用生物信息学方法可快速筛选出人类与大鼠肝癌发生发展过程中的共同关键基因以及与肝癌发生发展密切相关的通路。

Objective To use bioinformatics methods to analyze large amounts of data generated by gene chips and to screen common key genes in hepatocellular carcinoma in human and rat. Methods For search of the medical literature, 3 sets of gene chip with data which met our predetermined criteria were downloaded from the GEO database. The data were standardized by using the bioconductor and R version of the 2.10.1 version. The original data of the affymetrix platform were normalized with back- ground correction, standardized and transformed into log2 by using the algorithm of the affy packages RMA. The TTEST function of the excel was then used to calculate the significance of each gene. The DAVID was used for gene ID conversion and a table was established for samples and the corresponding gene expression data. A meta analysis was performed to calculate the common genes of human and rat. An enrichment regulation pathway was gained with the KEGG in the DAVID library. Results There were 26 common expression genes in the development process of hepatocellular carcinoma in hu- man and rat. Five of these genes were up-regulation genes, while twenty-one were down-regulation genes. An enrichment pathway, which is a focal adhesion pathway, was found and this pathway has been reported to be associated with development of hepatocellular carcinoma. Conclusion With bioin- formatics, we were able to screen common key genes and a pathway which were closely related to de- velopment of hepatocellular carcinoma in human and rat.