Version 1
: Received: 1 October 2020 / Approved: 2 October 2020 / Online: 2 October 2020 (15:21:34 CEST)
Version 2
: Received: 10 December 2020 / Approved: 11 December 2020 / Online: 11 December 2020 (18:12:38 CET)
Version 3
: Received: 16 February 2021 / Approved: 17 February 2021 / Online: 17 February 2021 (12:58:18 CET)
How to cite:
KP, M.; Wlochowitz, D.; Wingender, E.; Beißbarth, T.; KEL, A. IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme. Preprints2020, 2020100046. https://doi.org/10.20944/preprints202010.0046.v2
KP, M.; Wlochowitz, D.; Wingender, E.; Beißbarth, T.; KEL, A. IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme. Preprints 2020, 2020100046. https://doi.org/10.20944/preprints202010.0046.v2
KP, M.; Wlochowitz, D.; Wingender, E.; Beißbarth, T.; KEL, A. IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme. Preprints2020, 2020100046. https://doi.org/10.20944/preprints202010.0046.v2
APA Style
KP, M., Wlochowitz, D., Wingender, E., Beißbarth, T., & KEL, A. (2020). IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme. Preprints. https://doi.org/10.20944/preprints202010.0046.v2
Chicago/Turabian Style
KP, M., Tim Beißbarth and ALEXANDER KEL. 2020 "IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme" Preprints. https://doi.org/10.20944/preprints202010.0046.v2
Abstract
Only two percent of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survives less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that co-occur with aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. In this paper we applied upstream analysis approach which involves state-of-art promoter analysis and network analysis of the dysregulated genes potentially responsible for short survival in GBM. Transcription factors associated with GBM pathology like NANOG, NF-κB, REST, FRA-1, PPARG and seven others were found enriched in regulatory regions of the dysregulated genes. Based on network analysis, we propose novel gene regulatory network regulated by five master regulators – IGFBP2, VEGFA, VEGF165, PDGFA, AEBP1 and OSMR which can potentially act as therapeutic targets for enhancing GBM prognosis. Critical analysis of this gene regulatory network gives insights on mechanism of gene regulation by IGFBP2 via several transcription factors including the key molecule of GBM tumor invasiveness and progression FRA-1. All the observations are validated in independent cohorts and their impact on overall is studied on TCGA-GBM RNA seq data.
Keywords
Glioblastoma; master regulators; upstream analysis; IGFBP2; FRA-1; short term survivors; transcription factors
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
