Identification of key regulators in prostate cancer from gene expression datasets of patients

• Type of Material: Article
• Authors: Irengbam Rocky Mangangcha, Jamia Hamdard; Md. Zubbair Malik, Jawaharlal Nehru University; Omer Kucuk, Emory University; Shakir Ali, Jamia Hamdard; R. K. Brojen Singh, Jawaharlal Nehru University
• Language: English
• Date: 2019-11-11
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-019-52896-x
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 9
• Issue: 1
• Start Page: 16420
• End Page: 16420
• Grant/Funding Information: S.A. and O.K. acknowledge Indian Council of Medical Research for International fellowship to SA to visit Emory Winship Cancer Institute, Atlanta.; M.Z.M. acknowledges financial assistance from Department of Health Research, Ministry of Health and Family Welfare, Government of India under Young Scientist scheme (Sanction File No. R.12014/01/2018-HR, FTS No. 3146887).; R.K.B.S. acknowledges Jawaharlal Nehru University and UGC for UPE-II (Sanction no. 101) for financial assistance.; S.A. acknowledges the Department of Biotechnology, Ministry of Science and Technology, Government of India for the bioinformatics facility at Jamia Hamdard under BTISNet, the Biotechnology Information System Network (Sanction no. BT/BI/25/062/2012(BIF).
• Keywords: MECHANISMS; Multidisciplinary Sciences; NETWORK MOTIFS; COLORECTAL-CANCER; CENTRALITY; CYTOSCAPE; INHIBITION; Science & Technology - Other Topics; RIBOSOMAL-PROTEINS; PROLIFERATION; P53; Science & Technology; PROGRESSION
• Research Categories: Health Sciences, Oncology

Abstract

Identification of key regulators and regulatory pathways is an important step in the discovery of genes involved in cancer. Here, we propose a method to identify key regulators in prostate cancer (PCa) from a network constructed from gene expression datasets of PCa patients. Overexpressed genes were identified using BioXpress, having a mutational status according to COSMIC, followed by the construction of PCa Interactome network using the curated genes. The topological parameters of the network exhibited power law nature indicating hierarchical scale-free properties and five levels of organization. Highest degree hubs (k ≥ 65) were selected from the PCa network, traced, and 19 of them was identified as novel key regulators, as they participated at all network levels serving as backbone. Of the 19 hubs, some have been reported in literature to be associated with PCa and other cancers. Based on participation coefficient values most of these are connector or kinless hubs suggesting significant roles in modular linkage. The observation of non-monotonicity in the rich club formation suggested the importance of intermediate hubs in network integration, and they may play crucial roles in network stabilization. The network was self-organized as evident from fractal nature in topological parameters of it and lacked a central control mechanism.