皮肤鳞状细胞癌免疫细胞浸润与基因富集分析

Analysis of Immune Cell Infiltration and Gene Enrichment in Cutaneous Squamous Cell Carcinoma

目的通过生物信息学方法分析皮肤鳞状细胞癌(CSCC)中免疫细胞浸润相关基因差异表达及其意义。方法从基因表达数据库(GEO)搜索并下载CSCC数据集,经过检索及筛选得到临床信息GSE45216和GSE108008两个数据集,使用R语言CIBERSORT函数分析免疫细胞浸润情况,以及它们在CSCC组和对照组中的差异性。使用vioplot软件绘制差异细胞的小提琴图,R软件clusterProfiler包对靶基因通过基因本体(GO)功能注释和基于京都基因与基因组百科全书(KEGG)通路数据库进行信号通路富集分析。结果与对照组相比,CSCC组中380个差异表达基因,其中76个上调基因、304个下调基因,通过分析差异表达基因筛选排名前10的关键基因分别为人乳铁蛋白、G蛋白偶联受体1、RPTN、天冬氨酰氨基葡糖苷酶、PAN3、烟酰胺N-甲基转移酶、分泌粒蛋白5、叶酸受体3、维甲酸诱导蛋白14、多肽N-乙酰半乳糖氨基转移酶14;CSCC发生发展中导致浆细胞数量增加,M1型巨噬细胞数量减少,记忆性CD4+T细胞为高浸润性,且细胞溶解活性与嗜酸粒细胞呈正相关(r=0.530,P<0.001),而与M2型巨噬细胞呈显著负相关(r=-0.570,P<0.001),影响CSCC预后。GO富集分析显示,基因功能主要与角质细胞分化、细胞防御、存在于细胞膜或细胞核内的蛋白酶体有关。KEGG信号通路富集显示,差异表达基因主要参与胆固醇代谢、脂肪酸等脂质代谢通路。结论部分免疫细胞浸润及其相关基因差异表达在CSCC发生过程及其预后中起重要作用,角质细胞分化、脂质代谢信号通路改变可能与CSCC的发病机制密切相关。

Objective To analyze the differential expression and significance of genes related to immune cell infiltration in cutaneous squamous cell carcinoma(CSCC)by bioinformatics.Methods The CSCC dataset was searched and downloaded from the gene expression omnibus(GEO)database,and two datasets GSE45216 and GSE108008 were obtained by searching and screening.The infiltration of tumor infiltrating immune cells,as well as its difference between the CSCC group and control group,was analyzed by R language CIBERSORT function.The violin diagram of the differential cells was drawn by vioplot software.R software clusterProfiler package was used to analyze the signal pathway enrichment of target genes through Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database.Results Ccompared with the control group,there were 380 differentially expressed genes in CSCC group,including 76 up-regulated genes and 304 down-regulated genes.The top 10 key genes were human lactoferrin,G protein-coupled receptor 1,RPTN,aspartyl-glucosaminidase,PAN3,nicotinamide N-methyltransferase,secretogranin 5,folate receptor 3,retinoic acid induced protein 14 and peptide N-acetylgalactosaminyltransferase 14.During the occurrence and development of CSCC,the number of plasma cells increased,the number of M1 macrophages decreased,memory CD4+T cells were highly invasive,and the cytolytic activity was positively correlated with eosinophils(r=0.530,P<0.001),but negatively correlated with M2 macrophages(r=-0.570,P<0.001),affecting the prognosis of CSCC.GO enrichment analysis showed that gene function was mainly related to keratinocyte differentiation,cell defense and proteasome in cell membrane or nucleus.KEGG signal pathway enrichment showed that differentially expressed genes were mainly involved in cholesterol metabolism,fatty acids and other lipid metabolism pathways.Conclusion Some immune cell infiltration and differential expression of related genes play an important role in the pathogenesis and prognosis of CSCC.Keratinocyte differentiation and changes of lipid metabolism signal pathway may be closely related to the pathogenesis of CSCC.