CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Identification of key genes and immune infiltration in multiple myeloma by bioinformatics analysis.
Identification of key genes and immune infiltration in multiple myeloma by bioinformatics analysis.
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靶向 CD24 和 PTPRC 作为 MM 的分子标志物对 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。
多发性骨髓瘤（MM）是一种分子机制尚不明确的血液系统恶性肿瘤。本整合生物信息学研究旨在识别MM中的关键基因、通路和免疫细胞浸润模式。
使用R包'limma'筛选GSE6477和GSE16558数据集的差异表达基因（DEGs），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）和逻辑回归模型中筛选关键基因。使用survival和survminer包评估关键基因与MM生存之间的相关性。此外，通过CIBERSORT工具完成免疫浸润分析。
从两个GSE数据集中鉴定出118个DEGs（92个上调，26个下调），这些DEGs与B细胞受体信号通路和Epstein-Barr病毒感染密切相关。此外，通过logistic回归模型进一步筛选出PPI网络中鉴定出的五个hub基因中的CD24和PTPRC。此外，CD24和PTPRC的表达与MM患者的生存时间显著相关。最后，MM可能导致不同的浸润免疫细胞组成，包括B细胞记忆细胞、浆细胞、CD4记忆静息T细胞、滤泡辅助T细胞、Tregs、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，以及初始B细胞、初始CD4 T细胞、M2巨噬细胞和中性粒细胞的比例降低。
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.
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