Abstract
Background: Kashin-Beck disease (KBD) is currently an endemic form of osteoarthritis. In this study, we explored novel KBD diagnostic biomarkers.Methods: The GSE59446 dataset was used to conduct Weighted Gene Co-expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis with peripheral blood samples of 100 healthy individuals and 100 KBD patients. As part of the gene ontology pathway enrichment analysis, genes related to SONFH and DEGs were selected from the extraction module. Then, central DEGs were selected for LASSO analysis, and, based on SVM-RFE and DEG results, overlapping genes were identified as key KBD genes. Next, we analyzed the correlations between the selected genes and age, gender, and other factors to eliminate their influences on gene expression. Finally, we evaluated the diagnostic value of key KBD genes using case information collected by us.Results: Seven gene co-expression modules were created using WGCNA. The turquoise module was identified as a KBD key module since it showed the highest correlation to KBD. The functional enrichment analysis revealed that the genes associated with this key module were mainly involved in mitochondrial reactions, protein heterooligomerization, and negatively regulating cysteine-type endopeptidase-dependent apoptotic processes. Additionally, 12 key genes were identified using the LASSO analysis, 5 major genes using SVM-RFE analysis, and 36 DEGs were screened through the "limma" R package. The GLRX5 gene - pivotal in DEGs, LASSO, and SVM-RFE - was further aggregated as the key KBD gene. Correlation analyses confirmed the GLRX5 diagnostic value for KBD and that it was not related to age, gender, and other factors. Finally, data from our patients demonstrated that GLRX5 can be a KBD diagnostic biomarker.Conclusions: We demonstrated that the target gene GLRX5 can be a KBD non-invasive diagnosis biomarker.