Title:An Integrative Systems Analysis of High-grade Glioma Cell Lines: TLRs, Wnt, BRCA1, Netrins, STXBP1 and MDH1 Provide Putative Molecular Targets for Therapeutic Intervention
VOLUME: 11 ISSUE: 2
Author(s):Rekha Jain, Vinayak Pachapur, Aditi Kapoor, Meghana S. Vasavada, Prateek Singh, Durairaj Renu, Jyoti Bajpai Dikshit and Sanjeeva Srivastava
Affiliation:Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Mumbai- 400 076, India.
Keywords:High-grade glioma, Cell line, Systems biology, Pathways, Networks, Functional modules.
Abstract:Gliomas are the most common form of brain tumor, originate from glial cells and characterized by rapidly
proliferating cells frequently associated with an invasive phenotype. Several focused studies have successfully
demonstrated the genetic origin of these tumors; however, a systems level study to provide comprehensive overview of
complex molecular alterations associated with glioma pathogenesis is essential. In this study the main aim was to identify
molecular targets associated with high-grade gliomas using systems based investigation, and to identify pathways,
molecular networks and functional modules associated with curated genes/ proteins that have altered expression in highgrade
glioma cell lines. DAVID and PANTHER analysis tools were used to identify molecular functions, and functional
annotation clusters associated with curated dataset. IPA, MetaCore and GeneSpring were used to study the complex
interaction of curated molecules and identification of associated signaling pathways. The signaling pathways mediated by
TLRs, IL-8, STATs and Wnt, which regulate malignant behavior of high-grade gliomas, were identified as candidates for
therapeutic targets. STXBP1, PDK1, MAP3K8 and HIF1A/ARNT appeared as most significant modules in GeneSpring
functional analysis. GLIPR1 and MDH1 were identified as potential candidates for further study in gliomas. This study
represents a systems level approach to extract biologically relevant information from existing resources and provide new
contexts for future research in gliomas.
