Identification of key modules and hub genes for small-cell lung carcinoma and large-cell neuroendocrine lung carcinoma by weighted gene co-expression network analysis of clinical tissue-proteomes.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 11 01 2019
accepted: 03 05 2019
entrez: 6 6 2019
pubmed: 6 6 2019
medline: 1 2 2020
Statut: epublish

Résumé

Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.

Identifiants

pubmed: 31166966
doi: 10.1371/journal.pone.0217105
pii: PONE-D-19-01051
pmc: PMC6550379
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0217105

Déclaration de conflit d'intérêts

The funder provided support in the form of salaries for authors [YM and IT], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. YM and IT took part in this study with a purely scientific interest. The specific roles of these authors are articulated in the ‘author contributions’ section. The authors have declared that no competing interests exist. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

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Auteurs

Haruhiko Nakamura (H)

Department of Chest Surgery, St. Marianna University School of Medicine, Kanagawa, Japan.

Kiyonaga Fujii (K)

Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kanagawa, Japan.

Vipul Gupta (V)

The Systems Biology Institute, Tokyo, Japan.

Hiroko Hata (H)

Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Hirotaka Koizumu (H)

Department of Pathology, St. Marianna University Hospital, Kanagawa, Japan.

Masahiro Hoshikawa (M)

Department of Pathology, St. Marianna University Hospital, Kanagawa, Japan.

Saeko Naruki (S)

Department of Pathology, St. Marianna University Hospital, Kanagawa, Japan.

Yuka Miyata (Y)

Corporate Technology Research and Development, NISSHA Co., Kyoto, Japan.

Ikuya Takahashi (I)

Corporate Technology Research and Development, NISSHA Co., Kyoto, Japan.

Tomoyuki Miyazawa (T)

Department of Chest Surgery, St. Marianna University School of Medicine, Kanagawa, Japan.

Hiroki Sakai (H)

Department of Chest Surgery, St. Marianna University School of Medicine, Kanagawa, Japan.

Kouhei Tsumoto (K)

Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Masayuki Takagi (M)

Department of Pathology, St. Marianna University Hospital, Kanagawa, Japan.

Hisashi Saji (H)

Department of Chest Surgery, St. Marianna University School of Medicine, Kanagawa, Japan.

Toshihide Nishimura (T)

Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kanagawa, Japan.

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