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Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer

Dysregulation of signaling pathways plays an essential role in cancer. However, there is not a comprehensive understanding on how oncogenic signaling pathways affect the occurrence and development with a common molecular mechanism of pan-cancer. Here, we investigated the oncogenic signaling pathway...

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Autores principales: Wang, Na, He, Dan-Ni, Wu, Zhe-Yu, Zhu, Xu, Wen, Xiao-Ling, Li, Xu-Hua, Guo, Yu, Wang, Hong-Jiu, Wang, Zhen-Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428557/
https://www.ncbi.nlm.nih.gov/pubmed/36061170
http://dx.doi.org/10.3389/fgene.2022.916400
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author Wang, Na
He, Dan-Ni
Wu, Zhe-Yu
Zhu, Xu
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Wang, Hong-Jiu
Wang, Zhen-Zhen
author_facet Wang, Na
He, Dan-Ni
Wu, Zhe-Yu
Zhu, Xu
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Wang, Hong-Jiu
Wang, Zhen-Zhen
author_sort Wang, Na
collection PubMed
description Dysregulation of signaling pathways plays an essential role in cancer. However, there is not a comprehensive understanding on how oncogenic signaling pathways affect the occurrence and development with a common molecular mechanism of pan-cancer. Here, we investigated the oncogenic signaling pathway dysregulation by using multi-omics data on patients from TCGA from a pan-cancer perspective to identify commonalities across different cancer types. First, the pathway dysregulation profile was constructed by integrating typical oncogenic signaling pathways and the gene expression of TCGA samples, and four molecular subtypes with significant phenotypic and clinical differences induced by different oncogenic signaling pathways were identified: TGF-β+ subtype; cell cycle, MYC, and NF2− subtype; cell cycle and TP53+ subtype; and TGF-β and TP53− subtype. Patients in the TGF-β+ subtype have the best prognosis; meanwhile, the TGF-β+ subtype is associated with hypomethylation. Moreover, there is a higher level of immune cell infiltration but a slightly worse survival prognosis in the cell cycle, MYC, and NF2− subtype patients due to the effect of T-cell dysfunction. Then, the prognosis and subtype classifiers constructed by differential genes on a multi-omics level show great performance, indicating that these genes can be considered as biomarkers with potential therapeutic and prognostic significance for cancers. In summary, our study identified four oncogenic signaling pathway–driven patterns presented as molecular subtypes and their related potential prognostic biomarkers by integrating multiple omics data. Our discovery provides a perspective for understanding the role of oncogenic signaling pathways in pan-cancer.
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spelling pubmed-94285572022-09-01 Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer Wang, Na He, Dan-Ni Wu, Zhe-Yu Zhu, Xu Wen, Xiao-Ling Li, Xu-Hua Guo, Yu Wang, Hong-Jiu Wang, Zhen-Zhen Front Genet Genetics Dysregulation of signaling pathways plays an essential role in cancer. However, there is not a comprehensive understanding on how oncogenic signaling pathways affect the occurrence and development with a common molecular mechanism of pan-cancer. Here, we investigated the oncogenic signaling pathway dysregulation by using multi-omics data on patients from TCGA from a pan-cancer perspective to identify commonalities across different cancer types. First, the pathway dysregulation profile was constructed by integrating typical oncogenic signaling pathways and the gene expression of TCGA samples, and four molecular subtypes with significant phenotypic and clinical differences induced by different oncogenic signaling pathways were identified: TGF-β+ subtype; cell cycle, MYC, and NF2− subtype; cell cycle and TP53+ subtype; and TGF-β and TP53− subtype. Patients in the TGF-β+ subtype have the best prognosis; meanwhile, the TGF-β+ subtype is associated with hypomethylation. Moreover, there is a higher level of immune cell infiltration but a slightly worse survival prognosis in the cell cycle, MYC, and NF2− subtype patients due to the effect of T-cell dysfunction. Then, the prognosis and subtype classifiers constructed by differential genes on a multi-omics level show great performance, indicating that these genes can be considered as biomarkers with potential therapeutic and prognostic significance for cancers. In summary, our study identified four oncogenic signaling pathway–driven patterns presented as molecular subtypes and their related potential prognostic biomarkers by integrating multiple omics data. Our discovery provides a perspective for understanding the role of oncogenic signaling pathways in pan-cancer. Frontiers Media S.A. 2022-08-17 /pmc/articles/PMC9428557/ /pubmed/36061170 http://dx.doi.org/10.3389/fgene.2022.916400 Text en Copyright © 2022 Wang, He, Wu, Zhu, Wen, Li, Guo, Wang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wang, Na
He, Dan-Ni
Wu, Zhe-Yu
Zhu, Xu
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Wang, Hong-Jiu
Wang, Zhen-Zhen
Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title_full Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title_fullStr Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title_full_unstemmed Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title_short Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
title_sort oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428557/
https://www.ncbi.nlm.nih.gov/pubmed/36061170
http://dx.doi.org/10.3389/fgene.2022.916400
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