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Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV− HNSCC and to provide insights into potential regulatory mechanisms/effects within the a...

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Autores principales: Costa, Raquel L., Boroni, Mariana, Soares, Marcelo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189122/
https://www.ncbi.nlm.nih.gov/pubmed/30323202
http://dx.doi.org/10.1038/s41598-018-33498-5
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author Costa, Raquel L.
Boroni, Mariana
Soares, Marcelo A.
author_facet Costa, Raquel L.
Boroni, Mariana
Soares, Marcelo A.
author_sort Costa, Raquel L.
collection PubMed
description The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV− HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter. Weighted correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three distinct co-expression modules were associated with HPV status and molecular signatures. Validation using independent studies reporting biological experimental data converged for the most significant genes in all modules. This study provides insights into complex genetic and epigenetic particularities in the development and progression of HNSCC according to HPV status, and contribute to unveiling specific genes/pathways as novel therapeutic targets in HNSCC.
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spelling pubmed-61891222018-10-22 Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer Costa, Raquel L. Boroni, Mariana Soares, Marcelo A. Sci Rep Article The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV− HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter. Weighted correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three distinct co-expression modules were associated with HPV status and molecular signatures. Validation using independent studies reporting biological experimental data converged for the most significant genes in all modules. This study provides insights into complex genetic and epigenetic particularities in the development and progression of HNSCC according to HPV status, and contribute to unveiling specific genes/pathways as novel therapeutic targets in HNSCC. Nature Publishing Group UK 2018-10-15 /pmc/articles/PMC6189122/ /pubmed/30323202 http://dx.doi.org/10.1038/s41598-018-33498-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Costa, Raquel L.
Boroni, Mariana
Soares, Marcelo A.
Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title_full Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title_fullStr Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title_full_unstemmed Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title_short Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
title_sort distinct co-expression networks using multi-omic data reveal novel interventional targets in hpv-positive and negative head-and-neck squamous cell cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189122/
https://www.ncbi.nlm.nih.gov/pubmed/30323202
http://dx.doi.org/10.1038/s41598-018-33498-5
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