Development and validation of a genomic nomogram based on a ceRNA network for comprehensive analysis of obstructive sleep apnea

Abstract

Objectives: Some ceRNA associated with lncRNA have been considered as possible diagnostic and therapeutic biomarkers for obstructive sleep apnea (OSA). We intend to identify the potential hub genes for the development of OSA, which will provide a foundation for the study of the molecular mechanism underlying OSA and for the diagnosis and treatment of OSA. Methods: We collected plasma samples from OSA patients and healthy controls for the detection of ceRNA using a chip. Based on the differential expression of lncRNA, we identified the target genes of miRNA that bind to lncRNAs. We then constructed lncRNA-related ceRNA networks, performed functional enrichment analysis and protein-protein interaction analysis, and performed internal and external validation of the expression levels of stable hub genes. Then, we conducted LASSO regression analysis on the stable hub genes, selected relatively significant genes to construct a simple and easy-to-use nomogram, validated the nomogram, and constructed the core ceRNA sub-network of key genes. Results: We successfully identified 282 DElncRNAs and 380 DEmRNAs through differential analysis, and we constructed an OSA-related ceRNA network consisting of 292 miRNA-lncRNAs and 41 miRNA-mRNAs. Through PPI and hub gene selection, we obtained 7 additional robust hub genes, CCND2, WT1, E2F2, IRF1, BAZ2A, LAMC1, and DAB2. Using LASSO regression analysis, we created a nomogram with four predictors (CCND2, WT1, E2F2, and IRF1), and its area under the curve (AUC) is 1. Finally, we constructed a core ceRNA sub-network composed of 74 miRNA-lncRNA and 7 miRNA-mRNA nodes. Conclusion: Our study provides a new foundation for elucidating the molecular mechanism of lncRNA in OSA and for diagnosing and treating OSA.

Keywords: biomarkers; ceRNA; lncRNA; nomogram; obstructive sleep apnea.