Kulshrestha Anurag, Suman Shikha, Ranjan Rakesh
Bioinformatics Division, National Bureau of Animal Genetic Resources, Karnal.
Division of Applied Sciences, Indian Institute of Information Technology, Allahabad, India.
Onco Targets Ther. 2016 Jul 26;9:4569-81. doi: 10.2147/OTT.S108485. eCollection 2016.
Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein-protein interaction (PPI) and gene-gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs-microRNAs-transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings.
小儿肾上腺皮质癌(ACC)是一种罕见的恶性肿瘤,预后较差。小儿ACC发生和进展的分子机制尚不清楚。准确及时地诊断该疾病需要识别小儿ACC的新标志物。从小儿ACC的基因表达谱中鉴定出差异表达基因(DEG),这些数据来自基因表达综合数据库(Gene Expression Omnibus)。进行基因本体功能和通路富集分析以识别DEG的功能。构建了DEG的蛋白质-蛋白质相互作用(PPI)和基因-基因功能相互作用(GGI)网络。进行了枢纽基因检测和功能模块富集分析。此外,构建并分析了包含DEG-微小RNA-转录因子的基因调控网络。共筛选出431个DEG,其中包括228个上调的DEG和203个下调的DEG。这些基因主要参与细胞周期、类固醇生物合成和p53信号通路。上调基因CDK1、CCNB1、CDC20和BUB1B被确定为PPI和GGI网络的共同枢纽。所有这四个共同枢纽基因也是PPI网络模块的一部分。此外,所有这四个基因也存在于GGI网络的最大模块中。还构建了一个由82个微小RNA和100个转录因子组成的基因调控网络。CDK1、CCNB1、CDC20和BUB1B可能作为小儿ACC的潜在生物标志物以及治疗方法的潜在靶点,不过需要实验研究来验证我们的发现。