基于机器学习筛选膝骨关节炎基质组相关诊断标志物的研究

Abstract

Background It’s reported that matrisome exert a significant function in the pathogenesis of knee osteoarthritis (KOA). Thus, this study was conducted to screen the matrisome-associated diagnostic genes for KOA. Results : Total 158 matrisome-related genes in KOA were obtained, then 5 diagnostic genes were screened, namely collagen type 1 alpha 1 (COL1A1), high temperature requirement factor A1 (HTRA1), SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1 (SPOCK1), sulfatase 1 (SULF1) and extracellular matrix protein 1 (ECM1). These 5 diagnostic genes were both obviously overexpressed in KOA groups relative to those in healthy group, and both strongly associated with most immune cells, such as macrophage, eosinophil, and activated B cell. The targeted drugs for the 5 diagnostic genes contained 9-Octadecenamide, Diacerein, and Rifaximin. The mRNA and protein expression levels of the 5 diagnostic genes were consistent with the bioinformatics analysis results. Also, the viability of monosodium iodoacetate (MIA)-treated SW1353 cells was significantly decreased after upregulation of ECM1, while apoptosis showed the opposite trend. Moreover, MIA remarkably increased the phosphorylation levels of PI3K and Akt in SW1353 cells. Conclusions Five matrisome-associated diagnostic genes were identified with better diagnostic values, including COL1A1, HTRA1, SPOCK1, SULF1 and ECM1. ECM1 exacerbates the progression of KOA, and PI3K-Akt signaling pathway involved in the progression of KOA. The drugs, containing 9-Octadecenamide, Diacerein, and Rifaximin, etc., might be used for KOA treatment by targeting COL1A1, HTRA1, SPOCK1, SULF1 and ECM1.