胶质母细胞瘤中免疫和小胶质/巨噬细胞的特异性高表达基因具有间充质亚型的特性

Highly expressed specific genes of immune and microglia/macrophage cells in glioblastoma possess the feature of mesenchymal subtype

目的研究胶质母细胞瘤(GBM)中免疫细胞,特别是小胶质细胞/巨噬细胞中高表达的特异性基因集合,从而加深对胶质瘤中免疫微环境结构和功能的认识.方法在正常和GBM组织中,分析不同类型细胞中的分子表达情况,并得到免疫细胞和/或小胶质细胞/巨噬细胞(MM-Cells)中,特异性高表达的基因(MM-Genes).进一步研究MM-Genes在胶质瘤不同级别、不同分子亚型中的表达情况及对患者预后的影响.结果我们获得了一系列高度可靠的MM-Genes,包括CD74、HLA-DRB5、CCL3、NFAM1、DOCK8、LTC4S、GPR183、CCL4、SLAMF8、NCKAP1L、CD14、CD68、PLCB2.大部分MM-Genes在胶质瘤高表达,且随着级别而增加.另外,MM-Genes在GBM的间质亚型中高表达.其次,多数MM-Genes单个基因,以及MM-Genes的综合评分,均与患者预后相关,且高表达者预后差.结论MM-Genes与胶质瘤级别及GBM的间质亚型高度相关,且MM-Genes高表达者预后差,揭示了免疫调控与胶质瘤级别和分子亚型之间的关系.

Objective To investigate the specific gene sets highly expressed in immune cells,microglia/macrophages,in glioblastoma(GBM),in order to deepen the understanding of both structure and function of the immune microenvironment in glioblastoma.Methods Molecular expression levels in different types of cells in normal and GBM tissue were analyzed respectively,and genes specifically high expressed(MM-Genes)in immune and/or microglia/macrophages cells(MM-Cells)were acquired.Both expression levels of MM-Genes in different grades and molecular subtypes of gliomas,and impact of MM-Genes on patient prognosis,were further investigated.Results A series of highly reliable MM-Genes,including CD74,HLA-DRB5,CCL3,NFAM1,DOCK8,LTC4S,GPR183,CCL4,SLAMF8,NCKAP1L,CD14,CD68 and PLCB2 were obtained.The majority of MM-Genes were highly expressed in gliomas.In addition,the higher the grade of GBM was,the more expression of MM-Genes higher.Furthermore,MM-Genes were also highly expressed in the mesenchymal subtype of GBM.Secondly,most individual genes of MM-Genes,as well as the integrative score of MM-Genes(MM-GScore),were both associated with prognosis of patient.Patients with upregulated MM-GScore had poor prognosis.Conclusion MM-Genes were highly correlated with grade of glioma and mesenchymal subtype of GBM.High expression of MM-Genes revealed poor prognosis.It disclosed the relationship between immune regulation,glioma grade and molecular subtype.