Identification of key genes and molecular mechanism in hip joint capsule of patients with developmental dysplasia of the hip

Abstract

Abstract Developmental dysplasia of the hip(DDH) is a complex musculoskeletal congenital malformation, which is characterized by shallow acetabulum and laxity of joint capsule. While few studies have been conducted on the pathological changes of DDH joint capsule. Microarray technology can provide abundant gene expression information by bioinformatics analysis to predict diagnostic and therapeutic targets for DDH. Datasets GSE169494 downloaded from GEO were associated with DDH joint capsule. Weighted Gene Co-Expression Network Analysis was used for the initial gene module screening. Differentially expressed genes were obtained from R package DESeq2, which was set at the rate of P < 0.05, log FC >1.5 or < -1.5, then input into David for GO and KEGG enrichment to explore various biological characteristics. String database was utilized to construct protein-protein interaction network. Key genes were screened by plug-in Cytohubba of Cytoscape. 175 DEGs were mainly related to extracellular matrix metabolism and abnormal muscularization. Three key genes were obtained, including MMP3, COL3A1 and TCAP. ROC shows they all have diagnostic value(AUC=0.861, 0.917, 1.000). The pathogenesis of DDH is closely related to abnormal extracellular matrix metabolism, especially the process of collagen production and breakdown, which causes the repair and remodeling process of the extracellular matrix to slow down. And hip instability may contribute to abnormal muscularization of fibroblasts. Three key genes may be used as targets for diagnosis and therapy in DDH.