Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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
_version_ 1783570228703133696
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
work_keys_str_mv AT nishimuratoshihide aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT nakamuraharuhiko aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT tankienthiam aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT zhuodewei aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT fujiikiyonaga aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT koizumihirotaka aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT narukisaeko aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT takagimasayuki aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT furuyanaoki aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT katoyasufumi aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT chenshujen aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT katoharubumi aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT sajihisashi aproteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT nishimuratoshihide proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT nakamuraharuhiko proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT tankienthiam proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT zhuodewei proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT fujiikiyonaga proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT koizumihirotaka proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT narukisaeko proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT takagimasayuki proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT furuyanaoki proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT katoyasufumi proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT chenshujen proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT katoharubumi proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis
AT sajihisashi proteogenomicprofileofearlylungadenocarcinomasbyproteincoexpressionnetworkandgenomicalterationanalysis