Immune-related expression profiles of bisphosphonates-related osteonecrosis of the jaw in multiple myeloma

Objective: To investigate the immune cellular and genomic profiles of bisphosphonates-related osteonecrosis (BRONJ) of the jaw and excavate potential small molecule drugs. Methods and materials: The genomic profile of a multiple myeloma (MM) patient with BRONJ was downloaded from Gene Expression Omnibus (GEO). The 22 immune cell subsets infiltration in the patient were predicted by cell-type identification by estimating relative subsets of RNA transcripts. In addition, the differently expressed immune-related genes (DEMGs) of BRONJ were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for functional annotation. Then, potential drugs for BRONJ treatment were predicted by Connectivity Map (CMAP) based on DEGs. Results: High proportions of native CD4+T cells and M0 macrophages were observed while resting mast cells, NK cells, and eosinophils were downregulated in the BRONJ patient (P^< 0.05). Resting dendritic cells and gamma delta T cells were positively correlated (r=0.93). Additionally, 36 DEMGs were screened from 336 DEGs in BRONJ expression profiles. GO enrichment analysis revealed that DEMGs were most associated with peptidyl-tyrosine modification, myeloid leukocyte migration, leukocyte chemotaxis and regulation of chemokine production(P<0.05). KEGG analysis indicated that DEMGs were mainly related to cytokine-cytokine receptor interaction, IL-17 signaling pathway and NF-Kappa B signaling pathway(P<0.05). Besides, 12 small molecule drugs were screened in MM patient with ONJ. Conclusion: The discovery of different composition of immune cell types and immune-related transcriptomes in BRONJ helps to explain the onset and development of MRONJ, which provides a novel target for BRONJ therapy.