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

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 enhanc...

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Autores principales:	Leila Jahangiri, Perla Pucci, Tala Ishola, Joao Pereira, Megan L. Cavanagh, Suzanne D. Turner
Formato:	article
Lenguaje:	EN
Publicado:	Springer 2021
Materias:	Core regulatory circuitry Neuroblastoma Solid cancers Tumour microenvironment Gene networks Differentiation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/df223dd3d1b44677bf2909dbf1a754f3
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spelling	oai:doaj.org-article:df223dd3d1b44677bf2909dbf1a754f32021-12-05T12:26:27ZDeep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors10.1007/s12672-021-00452-32730-6011https://doaj.org/article/df223dd3d1b44677bf2909dbf1a754f32021-11-01T00:00:00Zhttps://doi.org/10.1007/s12672-021-00452-3https://doaj.org/toc/2730-6011Abstract 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.Leila JahangiriPerla PucciTala IsholaJoao PereiraMegan L. CavanaghSuzanne D. TurnerSpringerarticleCore regulatory circuitryNeuroblastomaSolid cancersTumour microenvironmentGene networksDifferentiationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENDiscover Oncology, Vol 12, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Core regulatory circuitry Neuroblastoma Solid cancers Tumour microenvironment Gene networks Differentiation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Core regulatory circuitry Neuroblastoma Solid cancers Tumour microenvironment Gene networks Differentiation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Leila Jahangiri Perla Pucci Tala Ishola Joao Pereira Megan L. Cavanagh Suzanne D. Turner Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
description	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.
format	article
author	Leila Jahangiri Perla Pucci Tala Ishola Joao Pereira Megan L. Cavanagh Suzanne D. Turner
author_facet	Leila Jahangiri Perla Pucci Tala Ishola Joao Pereira Megan L. Cavanagh Suzanne D. Turner
author_sort	Leila Jahangiri
title	Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
title_short	Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
title_full	Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
title_fullStr	Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
title_full_unstemmed	Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
title_sort	deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
publisher	Springer
publishDate	2021
url	https://doaj.org/article/df223dd3d1b44677bf2909dbf1a754f3
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Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

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