三阴性乳腺癌肿瘤微环境特征免疫相关生物学标志物筛选及功能预测分析  

Screening and functional prediction of immune-related biomarkers for tumor microenvironment characteristics of triple-negative breast cancer

作　　者：苏芃[1] 毛晓韵[1] 关舒[1] 崔梦遥 金紫凝 金锋[1] SU Peng;MAO Xiaoyun;GUAN Shu;CUI Mengyao;JIN Zining;JIN Feng(Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shengyan 110000,China)

机构地区：[1]中国医科大学附属第一医院乳腺外科,辽宁沈阳110000

出　　处：《中国肿瘤外科杂志》2020年第4期348-355,共8页Chinese Journal of Surgical Oncology

摘　　要：目的通过研究三阴性乳腺癌(TNBC)患者中的免疫微环境细胞浸润情况,从免疫微环境层面对TNBC患者的预后进行分析,提出新的TNBC免疫预后相关生物学标志物并描述其在TNBC中的生物学过程,为临床治疗TNBC提供新的治疗靶点。方法检索GEO TNBC相关公开数据库并下载样本的转录组学信息,通过CIBERSORT分析TNBC患者的免疫细胞成分,再通过无监督聚类对TNBC患者的免疫细胞成分进行聚类,寻找最佳的分类类型。采用差异基因分析探索TNBC中表达量异常的基因;通过lasso-logistic模型进行降维筛选免疫亚型的生物标志物;通过WGCNA进行基因共表达分析,并通过GSEA分析基因模块的主要富集的通路注释其参与的生物学过程。结果通过整理下载的GSE103091数据,共纳入包含mRNA数据和完整总生存数据TNBC患者100例,其免疫细胞成分可分两类:低免疫浸润组43例,其中转移19例(44.2%);高免疫浸润组57例,其中转移11例(19.3%),两组转移患者比例差异有统计学意义(χ^2=6.09,P=0.01)。低免疫浸润主要受到正向免疫调节相关通路和细胞刺激因子相关通路的调控,患者总生存较低,预后不良。通过Lasso-Logistic迭代特征选取算法分析发现,FOLH1、WDR18、LINC00638、OAS3、SETDB2可以很好地代表TNBC的免疫亚型,并且发现FOLH1、WDR18、LINC00638、OAS3、SETDB2可以作为预测TNBC患者预后的关键基因。结论在TNBC患者中FOLH1、WDR18、LINC00638、OAS3、SETDB2是重要的预后相关基因,并且通过T细胞激活等免疫调节相关通路影响患者预后。Objective By studying the infiltration of immune microenvironment cells in TNBC patients and analyzing the prognosis of TNBC patients from the perspective of immune microenvironment,new biological markers related to TNBC immune prognosis is proposed and theirs biological process in TNBC is described,which provides a new therapeutic target for clinical treatment of TNBC.Methods Search the GEO database related with TNBC and download the transcriptome information of the samples.Estimate the immune cell components of TNBC patients by CIBERSORT,and then cluster the immune cell components of TNBC patients by unsupervised clustering to find the best classification type.Differential gene analysis was used to explore genes with abnormal expression in TNBC;lasso logistic model was used to identify biomarkers of immune subtypes;WGCNA was used to analysis gene co expression,and GSEA was used to find out the main enriched pathways of gene module to explain the biological process involved.Results Downloaded GSE103091 data from Gene Expression Omnibus(GEO)database,100 cases of TNBC patients including mRNA data and complete total survival data were included.The immune cell components could be divided into two groups,43 patients in the low immune infiltration group including 19 patients with metastasis(44.2%);57 cases in the high immune infiltration group including 11 patients with metastasis(19.3%).There was a statistically significant difference between the two groups in the proportion of metastasis patients(χ^2=6.09,P=0.01).Low immune infiltration was mainly regulated by positive immune regulation related pathway and cell stimulating factor related pathway.The prognosis of patients in the group of Low immune infiltration was poor.Through the analysis of lasso logistic iterative feature selection algorithm,it was found that FOLH1,WDR18,LINC00638,OAS3 and SETDB2 can well represent the immune subtypes of triple negative breast cancer,and FOLH1,WDR18,LINC00638,OAS3 and SETDB2 can be used as the key genes to predict the prognosis

关 键 词：三阴性乳腺癌 免疫微环境 预后情况 生物信息学 

分 类 号：R73[医药卫生—肿瘤]