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Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data

2019; Impact Journals LLC; Volume: 10; Issue: 68 Linguagem: Inglês

10.18632/oncotarget.27204

1949-2553

Victor Menezes Silva, Jéssica Alves Gomes, Liliane Patrícia Gonçalves Tenório, Genilda Castro de Omena Neta, Karen da Costa Paixão, Ana Kelly Fernandes Duarte, Gabriel Cerqueira Braz da Silva, Ricardo Jansen Santos Ferreira, Bruna Del Vechio Koike, Carolinne de Sales Marques, Rafael Danyllo da Silva Miguel, Aline Cavalcanti de Queiroz, Luciana Xavier Pereira, Carlos Alberto de Carvalho Fraga,

Cancer Research and Treatments

// Victor Menezes Silva 1 , Jessica Alves Gomes 1 , Liliane Patrícia Gonçalves Tenório 1 , Genilda Castro de Omena Neta 1 , Karen da Costa Paixão 1 , Ana Kelly Fernandes Duarte 1 , Gabriel Cerqueira Braz da Silva 1 , Ricardo Jansen Santos Ferreira 1 , Bruna Del Vechio Koike 2 , Carolinne de Sales Marques 1 , Rafael Danyllo da Silva Miguel 1 , Aline Cavalcanti de Queiroz 1 , Luciana Xavier Pereira 1 and Carlos Alberto de Carvalho Fraga 1 1 Department of Medicine, Federal University of Alagoas, Campus Arapiraca, Brazil 2 Department of Medicine, Federal University of the São Francisco Valley, Petrolina, Brazil Correspondence to: Carlos Alberto de Carvalho Fraga, email: carlos.fraga@arapiraca.ufal.br Luciana Xavier Pereira, email: luxavierpereira@gmail.com Keywords: bioinformatic; lung squamous cell carcinoma; lung adenocarcinoma; neuroactive ligand-receptor interaction Received: June 17, 2019 Accepted: July 29, 2019 Published: December 31, 2019 ABSTRACT Schwann cells were identified in the tumor surrounding area prior to initiate the invasion process underlying connective tissue. These cells promote cancer invasion through direct contact, while paracrine signaling and matrix remodeling are not sufficient to proceed. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of Schwann cells associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. Gene set over-representation analyses was performed on core DEGs to identify significantly functional and pathway enrichment analysis between Schwann cells and, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). DEGs were further integrated with genome-scale human biomolecular networks. miRNAs were proposed by the reconstruction of a transcriptional and post-transcriptional regulatory network. Moreover, microarray-based transcriptome profiling was performed, and the prognostic power of selected dedifferentiated Schwann cell biomolecules was predicted. We observed that pathways associated with Schwann cells dedifferentiation was overexpressed in lung cancer samples. However, genes associated with Schwann cells migration inhibition system were downregulated. Besides, miRNA targeting those pathways were also deregulated. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer.