前列腺癌相关基因及功能的生物信息学分析

Bioinformatics analysis of prostate cancer related genes and its function

目的:利用生物信息学方法和体外实验,寻找前列腺癌发生的关键基因。方法:从GEO数据库下载基因芯片数据GSE60502,其中包括48例正常前列腺组织样本和47例前列腺癌组织样本。利用Morpheus(https:∥software.broadinstitute.org/morpheus/)在线工具分析前列腺癌组织和正常前列腺组织的差异表达基因,然后使用GCBI(https:∥www.GCBI.com.cn)在线进行差异表达基因的基因本体富集论(gene ontology,GO)分析、Pathway分析,对同时参与GO分析和Pathway分析的差异基因取交集,构建基因共表达网络和基因相互作用网络。最后通过CCK8实验进行验证。结果:共筛选出6 903个表达差异的基因,差异最大的前15个基因中,有上调基因9个,下调基因6个,其中表达差异最大的基因为CRISP3。GO分析提示差异基因主要参与的分子生物学过程包括小分子代谢过程、信号转导、DNA依赖的转录过程、RNA聚合酶Ⅱ启动子转录的正调节等。Pathway分析提示差异基因主要参与的通路包括PI3K-Akt信号通路、代谢途径、MAPK信号通路以及Wnt信号通路等。CACNA1A基因位于共表达网络的核心位置,而ADCY5、PIK3CB基因位于基因相互作用网络的核心位置。体外CCK8实验证实下调CACNA1A表达可明显抑制前列腺癌细胞增殖能力。结论:CRISP3、CACNA1A、ADCY5、PIK3CB基因可能是影响前列腺癌发生的关键基因。

Objective:To find the key genes in the occurrence of prostate cancer by using bioinformatics methods and in vitro experiments.Methods:Gene chip data GSE60502,including 48 normal prostate tissue samples and 47 prostate cancer tissue samples,was downloaded from the GEO database.The microarray date were analyzed by the online software Morpheus(https:∥software.broadinstitute.org/morpheus/),which displayed differentially expressed genes between these two kinds of samples.Then,GO enrichment and Pathway analysis of differentially expressed genes were performed by the GCBI,an online analysis tool.Gene co-expression network and gene interaction network were constructed using the common genes included in GO enrichment and Pathway analysis.Finally,cell proliferation was varified by the Cell Counting Kit-8.Results:A total of 6 903 differentially expressed genes were confirmed.The top15 genes include 9 up-regulated genes and 6 down-regulated genes,and the most differentially expressed gene was CRISP3.The differentially expressed genes were mostly involved in small molecule metabolic process,signal transduction,DNA-dependent transcription and positive regulation of transcription from RNA polymeraseⅡpromoter.The differentially expressed genes were mostly involved in Metabolic pathways,PI3 K-Akt signaling pathway,MAPK signaling pathway and Wnt signaling pathway.CACNA1A was at the centre of the co-expression network,while ADCY5 and PIK3CB were at the core of the gene interaction network.Down-regulation of CACNA1A could significantly inhibit cell proliferation in vitro.Conclusion:CRISP3,CACNA1A,ADCY5 and PIK3CB are probably the critical genes in the occurrence of prostate cancer.