Investigating the impact of Wnt pathway-related genes on biomarker and diagnostic model development for osteoporosis in postmenopausal females.

ABSTRACT

The Wnt signaling pathway is essential for bone development and maintaining skeletal homeostasis, making it particularly relevant in osteoporosis patients. Our study aimed to identify distinct molecular clusters associated with the Wnt pathway and develop a diagnostic model for osteoporosis in postmenopausal Caucasian women. We downloaded three datasets (GSE56814, GSE56815 and GSE2208) related to osteoporosis from the GEO database. Our analysis identified a total of 371 differentially expressed genes (DEGs) between low and high bone mineral density (BMD) groups, with 12 genes associated with the Wnt signaling pathway, referred to as osteoporosis-associated Wnt pathway-related genes. Employing four independent machine learning models, we established a diagnostic model using the 12 osteoporosis-associated Wnt pathway-related genes in the training set. The XGB model showed the most promising discriminative potential. We further validate the predictive capability of our diagnostic model by applying it to three external datasets specifically related to osteoporosis. Subsequently, we constructed a diagnostic nomogram based on the five crucial genes identified from the XGB model. In addition, through the utilization of DGIdb, we identified a total of 30 molecular compounds or medications that exhibit potential as promising therapeutic targets for osteoporosis. In summary, our comprehensive analysis provides valuable insights into the relationship between the osteoporosis and Wnt signaling pathway.