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

J 2021

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

JAHANGIRI, L., P. PUCCI, T. ISHOLA, J. PEREIRA, M.L. CAVANAGH et. al.

Basic information

Original name

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

Authors

JAHANGIRI, L., P. PUCCI, T. ISHOLA, J. PEREIRA, M.L. CAVANAGH and Suzanne Dawn TURNER (826 United Kingdom of Great Britain and Northern Ireland, guarantor, belonging to the institution)

Edition

DISCOVER ONCOLOGY, NEW YORK, SPRINGER, 2021, 1868-8497

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 0.000

RIV identification code

RIV/00216224:14740/21:00124300

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1007/s12672-021-00452-3

UT WoS

000723659800001

Keywords in English

Core regulatory circuitry; Neuroblastoma; Solid cancers; Tumour microenvironment; Gene networks; Differentiation

Abstract

V originále

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.

Citovat

JAHANGIRI, L., P. PUCCI, T. ISHOLA, J. PEREIRA, M.L. CAVANAGH and Suzanne Dawn TURNER. Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors. DISCOVER ONCOLOGY. NEW YORK: SPRINGER, 2021, vol. 12, No 1, p. 56-77. ISSN 1868-8497. Available from: https://dx.doi.org/10.1007/s12672-021-00452-3.

@article{1837279,
   author = {Jahangiri, L. and Pucci, P. and Ishola, T. and Pereira, J. and Cavanagh, M.L. and Turner, Suzanne Dawn},
   article_location = {NEW YORK},
   article_number = {1},
   doi = {http://dx.doi.org/10.1007/s12672-021-00452-3},
   keywords = {Core regulatory circuitry; Neuroblastoma; Solid cancers; Tumour microenvironment; Gene networks; Differentiation},
   language = {eng},
   issn = {1868-8497},
   journal = {DISCOVER ONCOLOGY},
   title = {Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors},
   url = {https://link.springer.com/article/10.1007/s12672-021-00452-3},
   volume = {12},
   year = {2021}
}

TY  - JOUR
ID  - 1837279
AU  - Jahangiri, L. - Pucci, P. - Ishola, T. - Pereira, J. - Cavanagh, M.L. - Turner, Suzanne Dawn
PY  - 2021
TI  - Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors
JF  - DISCOVER ONCOLOGY
VL  - 12
IS  - 1
SP  - 56
EP  - 56
PB  - SPRINGER
SN  - 18688497
KW  - Core regulatory circuitry
KW  - Neuroblastoma
KW  - Solid cancers
KW  - Tumour microenvironment
KW  - Gene networks
KW  - Differentiation
UR  - https://link.springer.com/article/10.1007/s12672-021-00452-3
N2  - 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.
ER  -

JAHANGIRI, L., P. PUCCI, T. ISHOLA, J. PEREIRA, M.L. CAVANAGH and Suzanne Dawn TURNER. Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors. \textit{DISCOVER ONCOLOGY}. NEW YORK: SPRINGER, 2021, vol.~12, No~1, p.~56-77. ISSN~1868-8497. Available from: https://dx.doi.org/10.1007/s12672-021-00452-3.

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