Open AccessIdentification 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
Author(s) -
Hiroki Nakamura,
Kiyonaga Fujii,
Vipul Gupta,
Hiroko Hata,
Hirotaka Koizumu,
Masahiro Hoshikawa,
Saeko Naruki,
Yuka Miyata,
Ikuya Takahashi,
Tomoki Miyazawa,
Hiroki Sakai,
Kouhei Tsumoto,
Masayuki Takagi,
Hisashi Saji,
Toshihide Nishimura
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0217105
Subject(s) - biology , chromatin remodeling , small cell lung carcinoma , gene expression , carcinogenesis , gene , heterogeneous nuclear ribonucleoprotein , cancer research , gene knockdown , proteome , computational biology , microbiology and biotechnology , rna splicing , genetics , carcinoma , rna , small cell carcinoma
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.