乳腺癌关键基因SDC1的临床预后意义及其与M1型巨噬细胞相关性分析

Clinical prognostic significance of key gene SDC1 in breast cancer and its correlation with M1 macrophages

目的通过生物信息学方法分析乳腺癌(Breast cancer,BC)关键基因SDC1,并分析其与M1型巨噬细胞的相关性。方法从GEO数据库下载3组BC芯片GSE42568、GSE71053和GSE8977数据,筛选其差异表达基因(Differential Expression Genes,DGEs),并进行基因本体(Gene Ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto Encyclopedia of Gene and Genome,KEGG)通路富集分析。利用STRING数据库和Cytoscape软件筛选DEGS中HUB基因。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载BC的RNAseq数据和相关临床信息,利用R语言对HUB基因进行单因素和多因素COX回归分析、列线图绘制以及关键基因的免疫检查点分析和风险预后分析;通过UALCAN与GEPIA数据库验证HUB基因的表达和预后;利用TIMER及GEPIA2021数据库进行关键基因与巨噬细胞相关性分析。结果共得到197个DEGs,其GO功能的生物学过程(BP)与细胞黏附、凋亡过程和细胞分化等有关,细胞成分(CC)主要富集在细胞外小体、细胞表面和染色质等位置,分子功能(MF)与锌离子结合、转录因子活性及整合素结合等相关,而KEGG通路主要富集在PI3K-Akt信号通路、黏着斑以及癌症中的蛋白聚糖等通路。通过逐步筛选得到BC的关键HUB基因SDC1,其在BC组织中高表达,且不利于患者预后。SDC1与SIGLEC15、IDO1、CD274,HAVCR2、CTLA4和PDCD1LG2等免疫检查点基因显著正相关(P<0.05),且也与巨噬细胞(r=0.189;P<0.05)以及M1型巨噬细胞(r=0.072;P<0.05)显著相关,同时也与M1型巨噬细胞标志物NOS2、CXCL10、IRF5、IL1A、IL1B、TLR2、TLR4、CD80及CD86等显著相关(P<0.05)。此外,高表达的M1型巨噬细胞显著利于BC患者的预后(P<0.05)。结论SDC1是BC的关键基因,并与M1型巨噬细胞显著相关,可成为BC潜在的免疫治疗靶点。

Objective To analyze the key gene SDC1 of breast cancer(BC)by bioinformatics methods,and its correlation with M1 macrophages.Methods Three sets of BC chips data GSE42568,GSE71053 and GSE8977 were downloaded from the GEO database,and their differential expression genes(DEGs)were screened,and functional annotation of gene ontology(GO)and pathway enrichment analysis of kyoto encyclopedia of gene and genome(KEGG)were also carried out.The HUB gene in DEGS was screened by STRING database and Cytascape software.Download the RNAseq data and relevant clinical information of BC from The Cancer Genome Atlas(TCGA),and R language was used to carry out single factor and multiple factor COX regression analysis,nomogram drawing,immune checkpoint analysis and risk prognosis analysis of HUB gene.The expression and prognosis of HUB gene were verified by UALCAN and GEPIA databases.The TIMER and GEPIA2021 databases were used to analyze the correlation between key genes and macrophages.Results A total of 197 DEGs were obtained.The biological process(BP)of their GO function was related to cell adhesion,apoptosis process,cell differentiation,etc.The cell component(CC)was mainly concentrated in extracellular bodies,cell surface,chromatin,etc.The molecular function(MF)was related to zinc ion binding,transcription factor activity and integrin binding,etc.The KEGG pathway was mainly concentrated in PI3K-Akt signal pathway,adhesion plaque,proteoglycan in cancer,etc.The key HUB gene SDC1 of BC was obtained through gradual screening,which washighly expressed in BC tissue and was not conducive to the prognosis of patients.SDC1 was significantly positivelycorrelated with SIGLEC15,IDO1,CD274,HAVCR2,CTLA4,PDCD1LG2 and other immune checkpoint genes(P<0.05).It is also associated with macrophages(r=0.189;P<0.05)and M1 macrophages(r=0.072;P<0.05)were significantly correlated with M1-type macrophage markers NOS2,CXCL10,IRF5,IL1A,IL1B,TLR2,TLR4,CD80 and CD86(P<0.05).In addition,the high expression of M1 type macrophages was significantly beneficial tothe prognosis of BC patients(P<0.05).Conclusions SDC1 is the key gene of BC,and is significantly associatedwith M1 type macrophages,which can be a potential immunotherapy target for BC.