Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme

Samreen Fathima; Swati Sinha; Sainitin Donakonda

doi:10.1016/j.csbj.2021.12.010

Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme

Comput Struct Biotechnol J. 2021 Dec 9:20:90-106. doi: 10.1016/j.csbj.2021.12.010. eCollection 2022.

Authors

Samreen Fathima¹, Swati Sinha¹, Sainitin Donakonda²

Affiliations

¹ Department of Biotechnology, Faculty of Life and Allied Health Sciences, MS Ramaiah University of Applied Sciences, Bangalore, India.
² Institute of Molecular Immunology and Experimental Oncology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.

Abstract

Glioblastoma multiforme persists to be an enigmatic distress in neuro-oncology. Its untethering capacity to thrive in a confined microenvironment, metastasize intracranially, and remain resistant to the systemic treatments, renders this tumour incurable. The glial cell type specificity in GBM remains exploratory. In our study, we aimed to address this problem by studying the GBM at the cell type level in the brain. The cellular makeup of this tumour is composed of genetically altered glial cells which include astrocyte, microglia, oligodendrocyte precursor cell, newly formed oligodendrocyte and myelinating oligodendrocyte. We extracted cell type-specific solid tumour as well as recurrent solid tumour glioma genes, and studied their functional networks and contribution towards gliomagenesis. We identified the principal transcription factors that are found to be regulating vital tumorigenic processes. We also assessed the protein-protein interaction networks at their domain level to get a more microscopic view of the structural and functional operations that transpire in these cells. This yielded the eminent protein regulators exhibiting their regulation in signaling pathways. Overall, our study unveiled regulatory mechanisms in glioma cell types that can be targeted for a more efficient glioma therapy.

Keywords: CAMs, Cell adhesion molecules; CNS, Cental nervous system; DEG, Differentially expressed genes; EMT, Epithelial-mesenchymal transistion; GBM, Glioblastoma multiforme; GSC, Glioblastoma Stem Cell; Glial cell types; Glioblastoma multiforme; INstruct, a database of structurally resolved protein interactome; MO, Myelinating oligodendrocyte; NCBI, National Centre for Biotechnology Information; NFO, Newly formed oligodendrocyte; NPC, Neural progenitor cell; OPC, Oligodendrocyte precursor cell; PDI, Protein domain interactions; PDIN, Protein domain interaction network; PPI, Protein-protein interactions; Primary solid tumour; Protein domains; Protein interaction networks; RSEM, RNA-seq by Expectation-Maximization; Recurrent solid tumour transcription factors; SIGNOR, Signaling Network Open Resource; TCGA, The Cancer Genome Atlas; TF, Transcription factor; TP, Primary solid tumour; TR, Recurrent solid tumour; WHO, World health organization; iDEP, Integrated Differential Expression and Pathway analysis.