Screening and validation for core genes in osteoarthritic cartilage based on weighted gene co-expression network analysis

- OBJECTIVE: Osteoarthritis (OA) has the highest disability rate among chron-ic diseases. The burden on patients and pub-lic health care resources is increasingly evident due to increasing obesity rates and aging popu-lations. So, there is still a lack of early diagnosis and treatment for OA. MATERIALS AND METHODS: A total of three OA cartilage tissue datasets (GSE1919, GSE32317, and GSE5235) were obtained from the Gene Ex-pression Omnibus (GEO) database. Screening of differentially expressed genes and WGCNA of overlapping genes were performed using the R language package. Functional and immune in-filtration analyses of overlapping genes were al- so carried out while hub genes were screened through LASSO regression analysis method and ROC curve. Finally, experimental validation was carried out through PCR and Western Blot analy-sis of rat cartilage. RESULTS: A total of 149 differentially ex-pressed genes were screened, and they were mainly enriched in the cytokine-cytokine recep-tor interaction, rheumatoid arthritis, and inter-leukin (IL-17) signaling pathways. Four co -ex-pression modules were obtained, of which the blue module was the most substantial morbidity associated with OA. Thirteen overlapping genes were identified based on significant module net- work topology analysis and differential genes, upon which their validation through LASSO re-gression analysis method and ROC curve was performed. From these, five signature genes were determined, before three potential core genes were finally identified after confirmation using the validation set. CONCLUSIONS: ATF3, FOSL2, and GADD45B may be hub genes to the osteochondropathy, and they are expected to be new biomarkers and drug targets in OA research.