Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer

Colorectal cancer (CRC) is driven in part by dysregulated Wnt, Ras-Raf-MAPK, TGF-β, and PI3K-Akt signaling. The progression of CRC is also promoted by molecular alterations and heterogeneous—yet interconnected—gene mutations, chromosomal instability, transcriptomic subtypes, and immune signatures. G...

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Autores principales:	Sha’Kayla K. Nunez, Corey D. Young, Ti’ara L. Griffen, Adaugo Q. Ohandjo, Lawrence P. McKinney, Scott Kopetz, James W. Lillard
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colorectal cancer (CRC) consensus molecular subtype (CMS) microsatellite stability (MSI) weighted gene co-expression network analysis (WGCNA) mitogen-activated protein kinase (MAPK) Integromics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/94961e74f9d24b23874c12cd25e289cc
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spelling	oai:doaj.org-article:94961e74f9d24b23874c12cd25e289cc2021-11-25T17:04:27ZIdentification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer10.3390/cancers132258242072-6694https://doaj.org/article/94961e74f9d24b23874c12cd25e289cc2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5824https://doaj.org/toc/2072-6694Colorectal cancer (CRC) is driven in part by dysregulated Wnt, Ras-Raf-MAPK, TGF-β, and PI3K-Akt signaling. The progression of CRC is also promoted by molecular alterations and heterogeneous—yet interconnected—gene mutations, chromosomal instability, transcriptomic subtypes, and immune signatures. Genomic alterations of CRC progression lead to changes in RNA expression, which support CRC metastasis. An RNA-based classification system used for CRC, known as consensus molecular subtyping (CMS), has four classes. CMS1 has the lowest survival after relapse of the four CRC CMS phenotypes. Here, we identify gene signatures and associated coding mRNAs that are co-expressed during CMS1 CRC progression. Using RNA-seq data from CRC primary tumor samples, acquired from The Cancer Genome Atlas (TCGA), we identified co-expression gene networks significantly correlated with CMS1 CRC progression. CXCL13, CXCR5, IL10, PIK3R5, PIK3AP1, CCL19, and other co-expressed genes were identified to be positively correlated with CMS1. The co-expressed eigengene networks for CMS1 were significantly and positively correlated with the TNF, WNT, and ERK1 and ERK2 signaling pathways, which together promote cell proliferation and survival. This network was also aligned with biological characteristics of CMS1 CRC, being positively correlated to right-sided tumors, microsatellite instability, chemokine-mediated signaling pathways, and immune responses. CMS1 also differentially expressed genes involved in PI3K-Akt signaling. Our findings reveal CRC gene networks related to oncogenic signaling cascades, cell activation, and positive regulation of immune responses distinguishing CMS1 from other CRC subtypes.Sha’Kayla K. NunezCorey D. YoungTi’ara L. GriffenAdaugo Q. OhandjoLawrence P. McKinneyScott KopetzJames W. LillardMDPI AGarticlecolorectal cancer (CRC)consensus molecular subtype (CMS)microsatellite stability (MSI)weighted gene co-expression network analysis (WGCNA)mitogen-activated protein kinase (MAPK)IntegromicsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5824, p 5824 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer (CRC) consensus molecular subtype (CMS) microsatellite stability (MSI) weighted gene co-expression network analysis (WGCNA) mitogen-activated protein kinase (MAPK) Integromics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer (CRC) consensus molecular subtype (CMS) microsatellite stability (MSI) weighted gene co-expression network analysis (WGCNA) mitogen-activated protein kinase (MAPK) Integromics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sha’Kayla K. Nunez Corey D. Young Ti’ara L. Griffen Adaugo Q. Ohandjo Lawrence P. McKinney Scott Kopetz James W. Lillard Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
description	Colorectal cancer (CRC) is driven in part by dysregulated Wnt, Ras-Raf-MAPK, TGF-β, and PI3K-Akt signaling. The progression of CRC is also promoted by molecular alterations and heterogeneous—yet interconnected—gene mutations, chromosomal instability, transcriptomic subtypes, and immune signatures. Genomic alterations of CRC progression lead to changes in RNA expression, which support CRC metastasis. An RNA-based classification system used for CRC, known as consensus molecular subtyping (CMS), has four classes. CMS1 has the lowest survival after relapse of the four CRC CMS phenotypes. Here, we identify gene signatures and associated coding mRNAs that are co-expressed during CMS1 CRC progression. Using RNA-seq data from CRC primary tumor samples, acquired from The Cancer Genome Atlas (TCGA), we identified co-expression gene networks significantly correlated with CMS1 CRC progression. CXCL13, CXCR5, IL10, PIK3R5, PIK3AP1, CCL19, and other co-expressed genes were identified to be positively correlated with CMS1. The co-expressed eigengene networks for CMS1 were significantly and positively correlated with the TNF, WNT, and ERK1 and ERK2 signaling pathways, which together promote cell proliferation and survival. This network was also aligned with biological characteristics of CMS1 CRC, being positively correlated to right-sided tumors, microsatellite instability, chemokine-mediated signaling pathways, and immune responses. CMS1 also differentially expressed genes involved in PI3K-Akt signaling. Our findings reveal CRC gene networks related to oncogenic signaling cascades, cell activation, and positive regulation of immune responses distinguishing CMS1 from other CRC subtypes.
format	article
author	Sha’Kayla K. Nunez Corey D. Young Ti’ara L. Griffen Adaugo Q. Ohandjo Lawrence P. McKinney Scott Kopetz James W. Lillard
author_facet	Sha’Kayla K. Nunez Corey D. Young Ti’ara L. Griffen Adaugo Q. Ohandjo Lawrence P. McKinney Scott Kopetz James W. Lillard
author_sort	Sha’Kayla K. Nunez
title	Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
title_short	Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
title_full	Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
title_fullStr	Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
title_full_unstemmed	Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer
title_sort	identification of gene co-expression networks associated with consensus molecular subtype-1 of colorectal cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/94961e74f9d24b23874c12cd25e289cc
work_keys_str_mv	AT shakaylaknunez identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT coreydyoung identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT tiaralgriffen identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT adaugoqohandjo identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT lawrencepmckinney identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT scottkopetz identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer AT jameswlillard identificationofgenecoexpressionnetworksassociatedwithconsensusmolecularsubtype1ofcolorectalcancer
_version_	1718412727244816384

Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer

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