Evaluation of Genes and Molecular Pathways Involved in the Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma: A Systems Biology Approach

Today, Monoclonal Gammopathy of Undetermined Significance (MGUS) is known as a plasma cell malignancy susceptible to evolving into the life-threatening stage, multiple myeloma (MM), without prominent clinical manifestations. Despite the discovery of advanced therapies and multiple pathogenic markers, the complexity of MM development has made it an incurable malignancy. In this study, the microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the LIMMA package of R-software to determine differentially expressed genes (DEGs) in MGUS and MM compared to the control samples. Enrichment analysis of DEGs was evaluated using the GeneCodis4 software. Protein-protein interaction (PPI) networks were constructed via the GeneMANIA database, and Cytoscape visualized them. The Molecular Complex Detection (MCODE) plugin from Cytoscape was used to identify the key modules from the PPI network. Afterward, the hub genes were recognized using the cytoHubba plug-in in Cytoscape. Eventually, the correlation between hub-DEGs and MM-specific survival was evaluated via the PrognoScan database. A total of 138 (MM-normal) and 136 (MGUS-normal) DEGs were obtained from the datasets, and 62 common DEGs between MGUS and MM diseases (26 up-regulated and 36 down-regulated genes) were screened out for subsequent analyses. Following enrichment analyses and the PPI network's evaluation, FOS, FOSB, JUN, MAFF, and PPP1R15A involved in the progression of MGUS to MM were detected as the hub genes. The survival analysis revealed that FOS, FOSB, and JUN among hub genes were significantly associated with disease-specific survival (DSS) in MM. Identifying the genes involved in the progression of MGUS to MM can help in the design of preventive strategies as well as the treatment of patients. In addition, their evaluation can be effective in the survival of patients.