Dataset Information

Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.

ABSTRACT: BACKGROUND:The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood. AIM:This study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms. METHODS:Tissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser capture microdissection (LCM). Transcriptomic analyses were performed and the results were confirmed by RT-PCR and immunohistochemistry in independent samples. RESULTS:After controlling for RNA quality, we analysed the transcriptomes of six cystic areas and five control areas. In total, 393 transcripts were differentially expressed in the epithelium, between CCAM and control areas. The most highly redundant genes involved in biological functions and signalling pathways differentially expressed between CCAM and control epithelium included TGFB2, TGFBR1, and MAP 2?K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples that TGFBR1 was more strongly expressed in CCAM than in control tissues (p?

SUBMITTER: Lezmi G

PROVIDER: S-EPMC7001206 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.

Lezmi Guillaume G Vibhushan Shamila S Bevilaqua Claudia C Crapart Nicolas N Cagnard Nicolas N Khen-Dunlop Naziha N Boyle-Freyssaut Christine C Hadchouel Alice A Delacourt Christophe C

Respiratory research 20200204 1

<h4>Background</h4>The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.<h4>Aim</h4>This study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms.<h4>Methods</h4>Tissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser captu ...[more]

PMID: 32019538

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Project description:ObjectivesTo explore the long non-coding RNA (lncRNA) expression pattern of congenital lung malformations on a genome-wide scale and investigate their potential biological function in four subtypes of congenital lung malformations.MethodsWe obtained both lesions and normal lung control tissues from the patients diagnosed with CPAM-I, CPAM-II, ILS, and ILS-CPAM, and underwent lobectomy (i.e., surgical removal of the whole lobe which contains the localized lesion as well as normal lung tissue). Then, we performed lncRNA transcriptome profiling in these tissues by RNA sequencing (RNA-seq). A comprehensive bioinformatics analysis was conducted to characterize the expression profiles and relevant biological functions and for multiple comparisons of lncRNA expression in the different subtypes of congenital lung malformation tissues. Furthermore, the lncRNA-mRNA co-expression network was constructed, and dysregulated mRNAs were functionally analyzed. Finally, gene set enrichment analysis (GSEA) was used to predict the potential molecular mechanism of the identified lncRNAs.ResultsA total of 5921 lncRNA transcripts were identified between congenital lung malformations tissues and normal lung control tissues. Compared with normal lung control, 481of these expressed lncRNAs were upregulated and 142 were downregulated in CPAM-I, 91 were upregulated and 14 were downregulated in CPAM-II, 39 were upregulated and 38 were downregulated in ILS, and 201 were upregulated and 38 were downregulated in ILS-CPAM. Unsupervised clustering and principal component analysis of the expressed lncRNAs visualized the differences between normal lung control and different subtypes of congenital lung malformations samples. We also confirmed significant differences in the composition of differentially expressed genes (DEGs) and the differentially expressed lncRNAs (DE lncRNAs) between CPAM-I and other subtypes of congenital lung malformations, as well as in normal lung control tissues, and observed enrichment of DEGs in the regulation of the immune system, cell projection organization, and inflammatory pathways. Finally, we identified the lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473.ConclusionsSignificant differences in lncRNAs expression patterns were observed between different subtypes of congenital lung malformations and normal control. The lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473.

Dataset Information

Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.

Publications

Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.

Similar Datasets

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