Systems Biology Approach for the Identification of Diagnostic and Therapeutic Targets in Medulloblastomas

Aditi      Kapoor; Vinayak      Pachapur; Rekha      Jain; Prateek      Singh; Durairaj      Renu; Jyoti Bajpai      Dikshit; Sanjeeva      Srivastava

doi:10.2174/1875692111311020006

Abstract

Medulloblastomas are the most aggressive pediatric brain tumors originating from self-renewing common progenitor cells and associated with high rate of invasion along with rapid spread. The hereditary origin of these tumors can be studied to define it at genome level; however, to understand the molecular mechanism and pathogenesis, systems level investigation is required. In this study we used systems level analysis to identify molecular targets, pathways, molecular networks and functional modules associated with genes/proteins with altered expression in medulloblastoma. Molecular functions, annotated functions, associated pathways, networks and functional modules were identified with PANTHER, DAVID, Ingenuity Pathway Analysis, MetaCore and GeneSpring software analysis, respectively. P53 signaling, PI3K/AKT signaling, Notch signaling, Hedgehog signaling and HGF signaling were identified as significant pathways, indicating the signature of molecules involved in medulloblastoma. Network analysis using IPA revealed new set of molecules, HNRNPK, PDE4A, HES5, GSTP1, SLC16A2, and GADD45A, which also appeared as significant functional modules in GeneSpring analysis. The systems biology approach used in this study provides a comprehensive understanding of complex molecular alterations involved in medulloblastoma and reveals potential novel targets, which could be used for future targeted or personalized therapeutic interventions.

Keywords: Cell lines, functional modules, medulloblastoma, molecular networks, personalized medicine, systems biology.