多发性骨髓瘤/浆细胞白血病差异表达基因生物学功能、关键基因表达水平及其与预后的关系

Biological function of differentially expressed genes,expression of core genes in multiple myeloma/plasma cell leukemia and their relationships with the prognosis

目的筛选出多发性骨髓瘤(MM)与浆细胞白血病(PCL)之间的差异表达基因,了解其生物学功能,明确关键基因表达水平与MM预后的关系。方法从公共基因芯片数据库(GEO)中下载MM与PCL芯片数据集GSE66291和GSE70323,在R软件中用Limma包分别筛选差异表达基因(DEGs)并取交集。利用基因本体(GO)以及京都基因与基因组百科全书(KEGG)信号通路分析对DEGs进行功能和通路注释,使用Sring对交集的DEGs构建蛋白质—蛋白质互作网络(PPI),筛选关键基因,使用Cytohubba插件筛选相关度前20位的关键基因,最后在GSE24080中根据关键基因的表达水平将MM患者分为高表达组及低表达组,比较高低表达组的总体生存率。结果共获取DEGs 389个,120个上调,269个下调。GO分析结果显示:在细胞组分方面主要与细胞膜外区域相关;在生物过程方面,参与白细胞游走、中性粒细胞聚集、体液免疫等;分子功能方面,主要与抗原结合相关。KEGG结果提示DEGs在细胞黏附分子、局灶性黏附等相关通路上富集。筛选出CDH1、CD44等20个关键基因,其中CXCL12、CDH1、RNASE3、LYZ、PPBP、VCAM1、QPCT、PECAM1与MM高表达组MM患者的总体生存率高于低表达组(P均<0.05)。结论MM与PCLD的DEGs中120个上调,269个下调。DEGs主要与细胞膜外区域相关,参与白细胞游走、与抗原结合、调控细胞黏附分子及局灶性黏附等相关通路。CXCL12、CDH1、RNASE3、LYZ、PPBP、VCAM1、QPCT和PECAM1可能是与MM患者预后相关的关键基因,其高表达组MM患者预后较好。

Objective To screen the differentially expressed genes(DEGs)between multiple myeloma(MM)and plasma cell leukemia(PCL),to understand their biological functions,and to clarify the relationship between expression of core genes and prognosis of MM.Methods The mi-croarry data of GSE66291 and GSE70323,which contained the information of MM and PCL patients,were downloaded from the Gene Expression Omnibus(GEO),the DEGs were screened by limma package in R software.Functional and pathway annotation of DEGs were conducted by using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis.The protein-protein interaction(PPI)network was constructed by String database;then,Cytohubba was used to select the top 20 related core genes.According to the expression levels of core genes in GSE13591,patients with MM were divided into the high expression and low expression group.Finally,the overall survival of the different expression groups was compared in GSE24080.Results Totally 389 DEGs were obtained,including 120 up-regulated genes and 269 down-regulated genes.The GO analysis results showed that the components of the cells were mainly related to the extracellular membrane region.In terms of biological processes,leukocyte migration,neutrophil aggregation and humoral immunity were the key regions of differential gene expression.In terms of molecular function,it was mainly related to antigen binding.KEGG results suggested that DEGs were enriched in cell adhesion molecules,focal adhesion and other related pathways.Twenty core genes were selected,such as CDH1 and CD44.Among those core genes,the overall survival of MM patient with CXCL12,CDH1,RNASE3,LYZ,PPBP,VCAM1,QPCT,and PECAM1 was significantly higher in the high expression group than in the low expression group(all P<0.05).Conclusions Among the DEGs of MM and PCL,120 up-regulated genes and 269down-regulated gene are found.DEGs are mainly related to the extracellular membrane region,and are involved in leukocyte migration,antigen binding,regulation of cell adhesion molecules,and focal adhesion.CXCL12,CDH1,RNASE3,LYZ,PPBP,VCAM1,QPCT and PECAM1 may be the core genes related to the prognosis of MM patients,and MM patients of the high expression group have better prognosis.