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Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA)

1
Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland
2
Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, 15-276 Bialystok, Poland
3
Department of Medical Pathomorphology, Medical University of Bialystok, 15-276 Bialystok, Poland
4
Department of Clinical Molecular Biology, Medical University of Bialystok, 15-276 Bialystok, Poland
5
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 37; https://doi.org/10.3390/cancers12010037
Received: 12 November 2019 / Revised: 16 December 2019 / Accepted: 19 December 2019 / Published: 21 December 2019
Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis and treatment of ADC and SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with the histological subtypes of NSCLC. The present study aims to identify the key dysregulated pathways and genes involved in the development of lung ADC and SCC and to relate them with the clinical traits. The transcriptional changes between tumour and normal lung tissues were investigated by RNA-seq. Gene ontology (GO), canonical pathways analysis with the prediction of upstream regulators, and weighted gene co-expression network analysis (WGCNA) to identify co-expressed modules and hub genes were used to explore the biological functions of the identified dysregulated genes. It was indicated that specific gene signatures differed significantly between ADC and SCC related to the distinct pathways. Of identified modules, four and two modules were the most related to clinical features in ADC and SCC, respectively. CTLA4, MZB1, NIP7, and BUB1B in ADC, as well as GNG11 and CCNB2 in SCC, are novel top hub genes in modules associated with tumour size, SUVmax, and recurrence-free survival. Our research provides a more effective understanding of the importance of biological pathways and the relationships between major genes in NSCLC in the perspective of searching for new molecular targets. View Full-Text
Keywords: non-small-cell lung cancer; squamous cell lung cancer; adenocarcinoma; transcriptomic profiling; next-generation sequencing; WGCNA non-small-cell lung cancer; squamous cell lung cancer; adenocarcinoma; transcriptomic profiling; next-generation sequencing; WGCNA
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MDPI and ACS Style

Niemira, M.; Collin, F.; Szalkowska, A.; Bielska, A.; Chwialkowska, K.; Reszec, J.; Niklinski, J.; Kwasniewski, M.; Kretowski, A. Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA). Cancers 2020, 12, 37. https://doi.org/10.3390/cancers12010037

AMA Style

Niemira M, Collin F, Szalkowska A, Bielska A, Chwialkowska K, Reszec J, Niklinski J, Kwasniewski M, Kretowski A. Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA). Cancers. 2020; 12(1):37. https://doi.org/10.3390/cancers12010037

Chicago/Turabian Style

Niemira, Magdalena, Francois Collin, Anna Szalkowska, Agnieszka Bielska, Karolina Chwialkowska, Joanna Reszec, Jacek Niklinski, Miroslaw Kwasniewski, and Adam Kretowski. 2020. "Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA)" Cancers 12, no. 1: 37. https://doi.org/10.3390/cancers12010037

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