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Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer

Breast cancer (BC) is the leading cause of cancer-related death in women. Therefore, a better understanding of BC biology and signaling pathways might lead to the development of novel biomarkers and targeted therapies. Although a number of transcriptomic studies have been performed on breast cancer...

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Autores principales: Vishnubalaji, Radhakrishnan, Sasidharan Nair, Varun, Ouararhni, Khalid, Elkord, Eyad, Alajez, Nehad M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759650/
https://www.ncbi.nlm.nih.gov/pubmed/31620367
http://dx.doi.org/10.3389/fonc.2019.00910
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author Vishnubalaji, Radhakrishnan
Sasidharan Nair, Varun
Ouararhni, Khalid
Elkord, Eyad
Alajez, Nehad M.
author_facet Vishnubalaji, Radhakrishnan
Sasidharan Nair, Varun
Ouararhni, Khalid
Elkord, Eyad
Alajez, Nehad M.
author_sort Vishnubalaji, Radhakrishnan
collection PubMed
description Breast cancer (BC) is the leading cause of cancer-related death in women. Therefore, a better understanding of BC biology and signaling pathways might lead to the development of novel biomarkers and targeted therapies. Although a number of transcriptomic studies have been performed on breast cancer patients from various geographic regions, there are almost no such comprehensive studies performed on breast cancer from patients in the gulf region. This study aimed to provide a better understanding of the altered molecular networks in BC from the gulf region. Herein, we compared the transcriptome of BC to adjacent normal tissue from six BC patients and identified 1,108 upregulated and 518 downregulated transcripts. A selected number of genes from the RNA-Seq analysis were subsequently validated using qRT-PCR. Differentially expressed (2.0-fold change, adj. p < 0.05) transcripts were subjected to ingenuity pathway analysis, which revealed a myriad of affected signaling pathways and functional categories. Activation of ERBB2, FOXM1, ESR1, and IGFBP2 mechanistic networks was most prominent in BC tissue. Additionally, BC tissue exhibited marked enrichment in genes promoting cellular proliferation, migration, survival, and DNA replication and repair. The presence of genes indicative of immune cell infiltration and activation was also observed in BC tissue. We observed high concordance [43.5% (upregulated) and 62.1% (downregulated)] between differentially expressed genes in our study group and those reported for the TCGA BC cohort. Our data provide novel insight on BC biology and suggest common altered molecular networks in BC in this geographic region. Our data suggest future development of therapeutic interventions targeting those common signaling pathways.
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spelling pubmed-67596502019-10-16 Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer Vishnubalaji, Radhakrishnan Sasidharan Nair, Varun Ouararhni, Khalid Elkord, Eyad Alajez, Nehad M. Front Oncol Oncology Breast cancer (BC) is the leading cause of cancer-related death in women. Therefore, a better understanding of BC biology and signaling pathways might lead to the development of novel biomarkers and targeted therapies. Although a number of transcriptomic studies have been performed on breast cancer patients from various geographic regions, there are almost no such comprehensive studies performed on breast cancer from patients in the gulf region. This study aimed to provide a better understanding of the altered molecular networks in BC from the gulf region. Herein, we compared the transcriptome of BC to adjacent normal tissue from six BC patients and identified 1,108 upregulated and 518 downregulated transcripts. A selected number of genes from the RNA-Seq analysis were subsequently validated using qRT-PCR. Differentially expressed (2.0-fold change, adj. p < 0.05) transcripts were subjected to ingenuity pathway analysis, which revealed a myriad of affected signaling pathways and functional categories. Activation of ERBB2, FOXM1, ESR1, and IGFBP2 mechanistic networks was most prominent in BC tissue. Additionally, BC tissue exhibited marked enrichment in genes promoting cellular proliferation, migration, survival, and DNA replication and repair. The presence of genes indicative of immune cell infiltration and activation was also observed in BC tissue. We observed high concordance [43.5% (upregulated) and 62.1% (downregulated)] between differentially expressed genes in our study group and those reported for the TCGA BC cohort. Our data provide novel insight on BC biology and suggest common altered molecular networks in BC in this geographic region. Our data suggest future development of therapeutic interventions targeting those common signaling pathways. Frontiers Media S.A. 2019-09-18 /pmc/articles/PMC6759650/ /pubmed/31620367 http://dx.doi.org/10.3389/fonc.2019.00910 Text en Copyright © 2019 Vishnubalaji, Sasidharan Nair, Ouararhni, Elkord and Alajez. http://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 Oncology
Vishnubalaji, Radhakrishnan
Sasidharan Nair, Varun
Ouararhni, Khalid
Elkord, Eyad
Alajez, Nehad M.
Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title_full Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title_fullStr Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title_full_unstemmed Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title_short Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer
title_sort integrated transcriptome and pathway analyses revealed multiple activated pathways in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759650/
https://www.ncbi.nlm.nih.gov/pubmed/31620367
http://dx.doi.org/10.3389/fonc.2019.00910
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