Abstract
Emerging studies demonstrated that miRNAs played fundamental roles in lung cancer. In this study, we attempted to explore the clinical significance of the miRNA signature in different histological subtypes of non-small cell lung cancer (NSCLC). Three miRNome profiling datasets (GSE19945, GSE25508 and GSE51853) containing lung squamous cell carcinoma (SCC), lung adenocarcinoma (ADC) and large cell lung cancer (LCLC) samples were obtained for bioinformatics and survival analysis. Moreover, pathway enrichment and coexpression network were performed to explore underlying molecular mechanism. MicroRNA-375 (miR-375), miR-203 and miR-205 were identified as differentially expressed miRNAs (DEmiRNAs) which distinguished SCC from other NSCLC subtypes. Pathway enrichment analysis suggested that Hippo signaling pathway was combinatorically affected by above mentioned three miRNAs. Coexpression analysis of three miRNAs and the Hippo signaling pathway related genes were conducted based on another dataset, GSE51852. Four hub genes (TP63, RERE, TJP1 and YWHAE) were identified as the candidate targets of three miRNAs, and three of them (TP63, TJP1 and YWHAE) were validated to be downregulated by miR-203 and miR-375, respectively. Finally, survival analysis further suggested the prognostic value of three-miRNA signature in SCC patients. Taken together, our study compared the miRNA profiles among three histological subtypes of NSCLC, and suggested that a three-miRNA signature might be potential diagnostic and prognostic biomarkers for SCC patients.
Highlights
Lung cancer remains the leading cause of cancer-related death both worldwide and in China [1, 2]
Three miRNome profiling datasets (GSE19945, GSE25508 and GSE51853) containing lung squamous cell carcinoma (SCC), lung adenocarcinoma (ADC) and large cell lung cancer (LCLC) samples were obtained for bioinformatics and survival analysis
We explored the differentially expressed miRNA (DEmiRNA) between SCC and other two histological subtypes of non-small cell lung cancer (NSCLC), LCLC and ADC
Summary
Lung cancer remains the leading cause of cancer-related death both worldwide and in China [1, 2]. Non-small cell lung cancer (NSCLC) including three main histological subtypes, lung squamous cell carcinoma (SCC), lung adenocarcinoma (ADC) and large cell lung cancer (LCLC), accounts for over 80% cases of lung cancer [3]. Increasing studies demonstrated that therapeutic effect varied in different histological www.impactjournals.com/oncotarget subtypes of NSCLC, suggesting that early confirmation of histology is of critical importance [4,5,6]. There are emerging researches into the biological features of different histological subtypes of NSCLC, but the fundamental molecular mechanisms remain elusive. Smoking is a much greater risk of SCC than of ADC [7]. A clear understanding of the differences from morphological to genetic levels between them will definitely have a positive effect on precise therapy
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