Identification of hub genes and biological process analysis of otosclerosis patients based on WGCNA analysis

Abstract Background： Otosclerosis is a primary bone disease caused by the bone labyrinth, resorption, and abnormal bone deposition. According to current research, it is a complex disease related to genetic and environmental factors. However, the molecular mechanism associated with otosclerosis has not been clearly revealed. Methods： The purpose of this study was to screen differentially expressed genes (DEGs) in otosclerosis patients and corresponding normal controls by RNA sequencing (RNA-Seq) and then deal with DEGS by weighted gene co-expression network analysis (WGCNA). Gene ontology (GO) enrichment, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis are used to analyze genes in modules of clinical significance. Results： We obtained 11 modules of WGCNA and identified turquoise modules with 184 genes, which were highly related to the phenotype (otosclerosis) of WGCNA. Protein-protein interaction (PPI) network was constructed by using Cytoscape. GO analysis showed that the turquoise module was related to the transcriptional regulation of RNA polymerase II promoter, nucleus, and protein binding, while KEGG and PEA analysis showed that the turquoise module was mainly enriched in nucleocytoplasmic transport. We obtained 10 hub genes, which were verified by HPA (The Human Protein Atlas) database. Among them, AZU1, CAMP, and MPO were highly expressed in normal bone marrow tissues, while the expression in otosclerosis patients was significantly down-regulated compared with the control group. Conclusion： This suggests that these molecules can be used as candidate markers to distinguish between otosclerosis patients and healthy people. Overall, our research shows that the three hub genes may play a key role in the occurrence and development of otosclerosis.