Scientific Reports ( IF 3.8 ) Pub Date : 2023-05-26 , DOI: 10.1038/s41598-023-35378-z
Cong Xu 1 , Meng Gao 2 , Junhua Zhang 2 , Yunfeng Fu 1, 2
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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.
中文翻译:

IL5RA 作为多发性骨髓瘤进展和治疗反应中的免疫原性细胞死亡相关预测因子
以前的研究表明,免疫原性细胞死亡相关模式在骨髓瘤中具有潜力。IL5RA 在骨髓瘤和免疫原性细胞死亡中的意义仍然未知。我们使用 GEO 数据分析了 IL5RA 表达、基因表达谱和与 IL5RA 水平相关的分泌蛋白基因。使用 ConsensusClusterPlus 和 pheatmap R 包进行免疫原性细胞死亡亚组分类。富集分析基于 GO/KEGG 分析。IL5RA-shRNA转染骨髓瘤细胞后,检测细胞增殖、凋亡和药物敏感性。P < 0.05 被认为具有统计学意义。IL5RA 在骨髓瘤和进展性冒烟型骨髓瘤中上调。我们观察到 PI3K-Akt 信号通路和高 IL5RA 组中自然杀伤细胞介导的细胞毒性等通路的富集。IL5RA 还与 CST6 等分泌蛋白基因密切相关。我们观察了免疫原性细胞死亡簇中差异基因上细胞凋亡和河马信号通路的富集。此外,IL5RA 与免疫浸润、免疫原性细胞死亡相关基因、免疫检查点相关基因和骨髓瘤中的 m6A 相关。体外和体内实验表明 IL5RA 参与骨髓瘤细胞的凋亡、增殖和耐药性。IL5RA 显示出成为骨髓瘤免疫原性细胞死亡相关预测因子的潜力。