OBJECTIVEThis study aims to utilize multiple bioinformatics tools to elucidate the potential mechanisms underlying the comorbidity of Multiple Myeloma (MM) and Osteonecrosis of the Femoral Head (ONFH).METHODHigh-throughput microarray datasets for MM and ONFH were retrieved from the GEO database, followed by separate preprocessing. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to construct co-expression networks within the MM datasets, further identifying modules and genes associated with MM clinical characteristics. Potential comorbid genes were enriched and analyzed using pathway and network analysis tools, and key genes for MM and ONFH comorbidity were preliminarily screened using Cytoscape. The gene expression capabilities and performance were validated using two disease-related datasets, and we evaluated the differences and consistencies in the immune microenvironment between the two diseases.RESULTSOur screening identified 418 immune-related comorbid genes, showing consistent biological processes in ribosome synthesis, particularly protein synthesis across both diseases. Key genes were further identified through Protein-Protein Interaction (PPI) networks, and their performance was validated in a validation cohort, with Receiver Operating Characteristic (ROC) curve areas exceeding 0.8. The immune microenvironment analysis highlighted consistent plasma cell infiltration correlated with disease comorbidity, suggesting potential immune targets for future therapies.CONCLUSIONMM and ONFH share common pathogenic genes that mediate changes in signaling pathways and immune cell dynamics, potentially influencing the comorbidity and progression of these diseases. Key genes identified, such as RPS19, RPL35, RPL24, RPL36, and EIF3G, along with plasma cell infiltration, may serve as central mechanisms in the development of both diseases. This study offers insights and references for further research into targeted treatments for these conditions.
