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.

Základní údaje

Originální název

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

Autoři

JAHANGIRI, L.; P. PUCCI; T. ISHOLA; J. PEREIRA; M.L. CAVANAGH a Suzanne Dawn TURNER

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.667

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/21:00124300

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

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

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 5. 2022 13:41, Mgr. Pavla Foltynová, Ph.D.

Anotace

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 a 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, roč. 12, č. 1, s. 56-77. ISSN 1868-8497. Dostupné z: https://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 = {https://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 a 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, roč.~12, č.~1, s.~56-77. ISSN~1868-8497. Dostupné z: https://doi.org/10.1007/s12672-021-00452-3.

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