Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

Jahangiri, Leila and Pucci, Perla and Ishola, Tala and Pereira, Joao and Cavanagh, Megan L. and Turner, Suzanne D. (2021) Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors. Discover Oncology, 12 (1). p. 56. ISSN 2730-6011

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Abstract

Aim: Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods: To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results: We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion: Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

Item Type: Article
Additional Information: ** From Springer Nature via Jisc Publications Router ** History: received 26-08-2021; accepted 16-11-2021; registration 19-11-2021; pub-electronic 29-11-2021; online 29-11-2021; collection 12-2021. ** Licence for this article: http://creativecommons.org/licenses/by/4.0/
Identification Number: https://doi.org/10.1007/s12672-021-00452-3
Dates:
DateEvent
16 November 2021Accepted
29 November 2021Published Online
Uncontrolled Keywords: Research, Core regulatory circuitry, Neuroblastoma, Solid cancers, Tumour microenvironment, Gene networks, Differentiation
Subjects: CAH01 - medicine and dentistry > CAH01-01 - medicine and dentistry > CAH01-01-03 - medicine by specialism
Divisions: Faculty of Health, Education and Life Sciences > Centre for Life and Sport Sciences (C-LASS)
SWORD Depositor: JISC PubRouter
Depositing User: JISC PubRouter
Date Deposited: 09 Dec 2021 13:32
Last Modified: 09 Dec 2021 13:32
URI: http://www.open-access.bcu.ac.uk/id/eprint/12486

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