Meta-Analysis Illustrates Role of Interferon-γ Signaling in Multiple Myeloma Pathogenesis

Background: Multiple myeloma (MM) is a clonal B cell neoplasia that comes from growth of malignant B cells in the bone marrow. Stromal cells, including inflammatory cells, in the bone marrow enable MM persistence and growth. MM is characterized by an uncoordinated cytokine system with an increase in proinflammatory cytokines. While proinflammatory cytokines are essential in mounting an anti-tumor response, they can also drive cancer progression. Ultimately, it is the effects of the cytokine milieu in the immune microenvironment that help determine MM development. While the role of IFNγ in MM remains mixed and unclear, our analysis suggests IFNγ plays an oncogenic role in MM and offers other insights to MM pathology. Methods: The National Center for Biotechnology Information (NCBI) GEO is an open database of more than 2 million samples of functional genomics experiments. The Search Tag Analyze Resource for GEO (STARGEO) platform allows for meta-analysis of genomic signatures of disease and tissue. We employed the STARGEO platform to search the Gene Expression Omnibus and performed meta-analysis on 517 peripheral blood samples from multiple myeloma patients using 97 healthy peripheral blood samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis (IPA) to help define the genomic signature of MM and identify disease pathways. We analyzed genes that showed statistical significance disease and control samples (p