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Network analysis reveals potential markers for pediatric adrenocortical carcinoma

Authors Kulshrestha A, Suman S, Ranjan R

Received 14 March 2016

Accepted for publication 10 June 2016

Published 26 July 2016 Volume 2016:9 Pages 4569—4581

DOI https://doi.org/10.2147/OTT.S108485

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Chang Liu

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Anurag Kulshrestha,1 Shikha Suman,2 Rakesh Ranjan1

1Bioinformatics Division, National Bureau of Animal Genetic Resources, Karnal, 2Division of Applied Sciences, Indian Institute of Information Technology, Allahabad, India


Abstract: 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.

Keywords: gene expression profiling, protein–protein interaction network, network module, gene–gene functional interaction network

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