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

• Published in: Scientific reports Vol. 13; no. 1; pp. 8528 - 12
• Main Authors: Xu, Cong, Gao, Meng, Zhang, Junhua, Fu, Yunfeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67/1857; 631/67/1990/804; AKT protein; Apoptosis; Cell death; Cell proliferation; Cytotoxicity; Drug resistance; Gene expression; Hippo Signaling Pathway; Humanities and Social Sciences; Humans; Immunogenic Cell Death; Immunogenicity; Interleukin-5 Receptor alpha Subunit - genetics; Mortality; multidisciplinary; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; N6-methyladenosine; Natural killer cells; Phosphatidylinositol 3-Kinases - metabolism; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - genetics; Statistical analysis; Transfection
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-35378-z

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.