肾上腺皮质癌相关差异表达基因的生物信息学分析

Bioinformatics analysis of differentially expressed genes related to adrenocortical carcinoma

目的利用生物信息学方法分析肾上腺皮质癌的基因芯片数据,筛选并验证肾上腺皮质癌发生相关的关键基因。方法从公共基因表达数据库下载肾上腺皮质癌相关芯片数据,应用R语言中的Limma程序包筛选差异表达基因,对差异表达基因进行功能富集分析、通路分析及蛋白互作网络构建,然后利用Cytoscape软件进行关键基因筛选,最后利用基因表达分析数据库验证关键基因的表达,并进行患者生存曲线分析。结果筛选出差异表达基因469个,上调基因253个,下调基因216个。通路分析显示差异基因主要富集在细胞周期、代谢途径、P53信号通路等。蛋白互作网络筛选出GAPDH、CDK1、CCNB1、AURKA、TOP2A及CDC20六个关键基因,这六个关键基因在肾上腺皮质癌中的表达均显著上升,且除了GAPDH外,其余五个关键基因与患者预后不良显著相关。结论筛选出的关键基因有助于我们进一步了解肾上腺皮质癌的发生机制,并且可用做肾上腺皮质癌早期检测的分子标记物和免疫治疗的潜在靶标。

Objective The gene chip data of adrenocortical carcinoma were analyzed by bioinformatics method to screen and verify the key genes related to the occurrence of adrenocortical carcinoma.Methods Microarray data related to adrenocortical carcinoma were downloaded from gene expression omnibus(GEO)database.The Limma package in R language was used to screen the differentially expressed genes.Functional enrichment analysis,pathway analysis and protein interaction network were performed for differentially expressed genes.The Cytoscape software was then used to screen for key genes.Finally,Gene Expression Profilling Interactive Analysis(GEPIA)was used to verify the Expression of key genes,and the patient survival curve was analyzed.Results A total of 469 differentially expressed genes were screened,of which 253 were up-regulated and 216 were down-regulated.KEGG pathway analysis showed that the differential genes were mainly enriched in cell cycle,metabolic pathway,p53 signal pathway and so on.Six key genes,GAPDH,CDK1,CCNB1,AURKA,TOP2A and CDC20,were screened by protein interaction network.The expression of these six key genes increased significantly in adrenocortical carcinoma,with the exception of GAPDH.The other five key genes were significantly associated with poor prognosis.Conclusions The selected key genes are helpful for us to further understand the mechanism of occurrence and development of adrenocortical carcinoma and may be used as a molecular marker for early detection of adrenocortical carcinoma and a potential target for immunotherapy.