Xu Fei, Li Ling, Jiang LiMei, Zhang Jing
Department of Hematology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.
Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.
Hematology. 2023 Dec;28(1):2264517. doi: 10.1080/16078454.2023.2264517. Epub 2023 Oct 10.
Multiple Myeloma (MM) is a hematologic malignant disease with unclear molecular mechanisms. This integrated bioinformatic study aimed to identify key genes, pathways and immune cell infiltration pattern in MM.
Differentially expressed genes (DEGs) from GSE6477 and GSE16558 dataset were filtrated with R package 'limma', whose function were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The key genes were selected from Protein-protein interaction network (PPI) and logistic regression model. The correlation between key genes and survival in MM was evaluated using the survival and survminer package. Additionally, immune filtration analysis was accomplished by CIBERSORT tools.
118 DEGs (92 up-regulated and 26 down-regulated) from two GSE datasets were identified, which were closely related with B cell receptor signaling pathway and Epstein-Barr virus infection. Furthermore, CD24 and PTPRC of five hub genes identified in PPI network were further screened out by the logistic regression model. Besides, CD24 and PTPRC expression were significantly correlated to the survival time in MM patients. Finally, MM might cause different infiltrating immune cell compositions, including increased infiltrations of B cells memory, Plasma cells, T cells CD4 memory resting, T cells follicular helper, Tregs, NK cells resting, Macrophages(M0/M1), Dendritic cells resting and Mast cells activating, and lower proportions of B cells naïve, T cells CD4 naïve, Macrophages M2 and Neutrophils.
Targeting CD24 and PTPRC as molecular markers of MM is valuable to MM therapy. Moreover, the immune cell infiltration will provide new insights into MM immunopathology.
多发性骨髓瘤(MM)是一种分子机制尚不清楚的血液系统恶性疾病。这项综合生物信息学研究旨在识别MM中的关键基因、信号通路和免疫细胞浸润模式。
使用R包“limma”筛选GSE6477和GSE16558数据集中的差异表达基因(DEG),并通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析探索其功能。从蛋白质-蛋白质相互作用网络(PPI)和逻辑回归模型中选择关键基因。使用生存和survminer包评估关键基因与MM患者生存之间的相关性。此外,通过CIBERSORT工具完成免疫过滤分析。
从两个GSE数据集中鉴定出118个DEG(92个上调和26个下调),它们与B细胞受体信号通路和EB病毒感染密切相关。此外,通过逻辑回归模型进一步筛选出PPI网络中鉴定的五个枢纽基因中的CD24和PTPRC。此外,CD24和PTPRC表达与MM患者的生存时间显著相关。最后,MM可能导致不同的免疫细胞浸润组成,包括记忆B细胞、浆细胞、静息CD4记忆T细胞、滤泡辅助性T细胞、调节性T细胞、静息NK细胞、巨噬细胞(M0/M1)、静息树突状细胞和活化肥大细胞的浸润增加,以及幼稚B细胞、幼稚CD4 T细胞、M2巨噬细胞和中性粒细胞的比例降低。
将CD24和PTPRC作为MM的分子标志物进行靶向治疗对MM治疗具有重要价值。此外,免疫细胞浸润将为MM免疫病理学提供新的见解。