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A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis
The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423934/ https://www.ncbi.nlm.nih.gov/pubmed/32788598 http://dx.doi.org/10.1038/s41598-020-70578-x |
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author | Nishimura, Toshihide Nakamura, Haruhiko Tan, Kien Thiam Zhuo, De-Wei Fujii, Kiyonaga Koizumi, Hirotaka Naruki, Saeko Takagi, Masayuki Furuya, Naoki Kato, Yasufumi Chen, Shu-Jen Kato, Harubumi Saji, Hisashi |
author_facet | Nishimura, Toshihide Nakamura, Haruhiko Tan, Kien Thiam Zhuo, De-Wei Fujii, Kiyonaga Koizumi, Hirotaka Naruki, Saeko Takagi, Masayuki Furuya, Naoki Kato, Yasufumi Chen, Shu-Jen Kato, Harubumi Saji, Hisashi |
author_sort | Nishimura, Toshihide |
collection | PubMed |
description | The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein–protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes. |
format | Online Article Text |
id | pubmed-7423934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74239342020-08-13 A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis Nishimura, Toshihide Nakamura, Haruhiko Tan, Kien Thiam Zhuo, De-Wei Fujii, Kiyonaga Koizumi, Hirotaka Naruki, Saeko Takagi, Masayuki Furuya, Naoki Kato, Yasufumi Chen, Shu-Jen Kato, Harubumi Saji, Hisashi Sci Rep Article The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein–protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes. Nature Publishing Group UK 2020-08-12 /pmc/articles/PMC7423934/ /pubmed/32788598 http://dx.doi.org/10.1038/s41598-020-70578-x Text en © The Author(s) 2020 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 Nishimura, Toshihide Nakamura, Haruhiko Tan, Kien Thiam Zhuo, De-Wei Fujii, Kiyonaga Koizumi, Hirotaka Naruki, Saeko Takagi, Masayuki Furuya, Naoki Kato, Yasufumi Chen, Shu-Jen Kato, Harubumi Saji, Hisashi A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title | A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title_full | A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title_fullStr | A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title_full_unstemmed | A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title_short | A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
title_sort | proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423934/ https://www.ncbi.nlm.nih.gov/pubmed/32788598 http://dx.doi.org/10.1038/s41598-020-70578-x |
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