Identification of pyroptosis-related diagnostic model relate to immune infiltration in osteoarthritis

Abstract

BackgroundOsteoarthritis (OA) is a common chronic diseases which were associated with aging and progressive joint dysfunction. Pyroptosis, a novel mode of cell death. The effect of pyroptosis on osteoarthritis (OA) progression is still in the exploratory stage, and the specific mechanism is unclear. MethodsOA data sets were obtained from the GEO databases website. Bioinformatics analysis was conducted to identify pyroptosis-related genes (PRGs), construct a pyroptosis-related diagnostic model, and identify subtypes. We established the random forest (RF) model as well as a nomogram of differentially expressed PRGs. The association between immunity and pyroptosis was comprehensively explored. Finally, the expression levels of 3 OA characteristic genes were verified by qRT-PCR and immunohistochemistry. ResultsSeven differentially expressed PRGs (CASP3, GPX4, NOD1, TIRAP, SCAF11, CASP4, and CASP9) were obtained by differential analysis to establish RF models, and three important OA genes (CASP9, TIRAP, and SCAF11) were obtained. ROC curve proved that the established model had high diagnostic accuracy. Based on the above three important PRGs, a high-precision nomogram model is constructed. Two PRG models are determined by consensus clustering method. The enrichment degree of immune cells in cluster A was higher than that in cluster B, suggesting that cluster A might be related to the occurrence and development of OA. GPX4 was found to be positively correlated with higher immune infiltration. Finally, the expression levels of 3 OA characteristic genes were verified by qRT-PCR and immunohistochemistry. ConclusionWe constructed an effective prognostic model according to PRGs in OA and integrated explored the association between pyroptosis and immunity-related elements. This article provides a strong point for investigating directed immunotherapy methods with novelty for OA.