IL5RA as an immunogenic cell death-related predictor in progression and therapeutic response of multiple myeloma

Abstract

Previous studies have shown the potential of immunogenic cell death-related modalities in myeloma. The significance of IL5RA in myeloma and immunogenic cell death remains unknown. We analyzed IL5RA expression, the gene expression profile, and secretory protein genes related to IL5RA level using GEO data. Immunogenic cell death subgroup classification was performed using the ConsensusClusterPlus and pheatmap R package. Enrichment analyses were based on GO/KEGG analysis. After IL5RA-shRNA transfection in myeloma cells, cell proliferation, apoptosis, and drug sensitivity were detected. P < 0.05 was considered statistically significant. IL5RA was upregulated in myeloma and progressed smoldering myeloma. We observed enrichment in pathways such as the PI3K-Akt signaling pathway, and Natural killer cell mediated cytotoxicity in the high-IL5RA group. IL5RA was also closely associated with secretory protein genes such as CST6. We observed the enrichment of cellular apoptosis and hippo signaling pathway on differential genes in the immunogenic cell death cluster. Furthermore, IL5RA was associated with immune infiltration, immunogenic cell death-related genes, immune-checkpoint-related genes, and m6A in myeloma. In vitro and in vivo experiments showed the involvement of IL5RA in apoptosis, proliferation, and drug resistance of myeloma cells. IL5RA shows the potential to be an immunogenic cell death-related predictor for myeloma.

Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis

“…IL5RA has been shown to be involved in immunogenic cell death, a form of cell death that stimulates an immune response against dead cell antigens. 49 It has been associated with various diseases, including asthma and multiple myeloma, and its expression has been found to be upregulated in these conditions. 49 , 50 KYNU is an enzyme involved in the kynurenine pathway.…”

“… 49 It has been associated with various diseases, including asthma and multiple myeloma, and its expression has been found to be upregulated in these conditions. 49 , 50 KYNU is an enzyme involved in the kynurenine pathway. 51 , 52 Dysregulation of this pathway has been associated with various diseases, including cancer and neurodegenerative disorders.…”