A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis
| Autor: | Masayuki Takagi, Kien Thiam Tan, Saeko Naruki, Shu-Jen Chen, Harubumi Kato, Hisashi Saji, Kiyonaga Fujii, Hirotaka Koizumi, Toshihide Nishimura, Haruhiko Nakamura, De-Wei Zhuo, Yasufumi Kato, Naoki Furuya |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Lung Neoplasms endocrine system diseases Angiogenesis Molecular biology Gene Dosage lcsh:Medicine Diseases Stem cells medicine.disease_cause 0302 clinical medicine Loss of Function Mutation Gene Regulatory Networks Protein Interaction Maps lcsh:Science Cancer Proteogenomics Multidisciplinary Molecular medicine Biological techniques Cell cycle Middle Aged Oncology Adenocarcinoma lipids (amino acids peptides and proteins) Female Cell biology Epithelial-Mesenchymal Transition Biophysics Adenocarcinoma of Lung Adenocarcinoma in Situ Biology Gene dosage Article 03 medical and health sciences medicine Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Loss function lcsh:R medicine.disease digestive system diseases Computational biology and bioinformatics 030104 developmental biology Risk factors Cancer research Neutrophil degranulation lcsh:Q Carcinogenesis 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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