基于生物信息学分析白血病抑制因子受体与乳腺癌预后的相关关系  

The correlation between LIFR and the prognosis of breast cancer based on bioinformatics

作　　者：田甜 邓飞[2] 唐金海 TIAN Tian;DENG Fei;TANG Jinhai(Clinical Medicine,Xuzhou Medical University, Xuzhou 221000, China;Department of General Surgery, the First Afliated Hospital of Nanjing Medical University, Nanjing 210029, China)

机构地区：[1]徐州医科大学临床学院,江苏徐州221000 [2]南京医科大学第一附属医院普外科,江苏南京210029

出　　处：《中国肿瘤外科杂志》2020年第4期338-347,共10页Chinese Journal of Surgical Oncology

基　　金：国家重点研发计划(2016YFC0905900);国家自然科学基金(81872365);江苏省社会发展“临床前沿技术”重点项目(BE2019731)。

摘　　要：目的通过生物信息学分析技术分析乳腺癌中白血病抑制因子受体(LIFR)对患者预后以及肿瘤微环境免疫细胞浸润的影响。方法通过Oncomine数据库和TIMER数据库分析LIFR在泛癌中的表达。通过UCSC Xena下载数据研究LIFR在不同肿瘤类型中与肿瘤突变负荷及微卫星不稳定性的关系。利用“ESTIMATE”R包评价LIFR与乳腺癌肿瘤微环境的相关性。使用PrognoScan和Kaplan-Meier plotter评估LIFR对乳腺癌患者临床预后的影响。进一步通过TISIDB数据库评价乳腺癌中LIFR在不同免疫亚型、分子亚型中的分布情况,并利用UALCAN数据库分析乳腺癌中LIFR启动子甲基化情况。此外,还利用RT-qPCR进一步证实LIFR在乳腺癌中的表达,通过划痕实验验证LIFR对乳腺癌细胞功能的影响。最后通过miRTarBase、TargetScan、microRNA.org、miRDB数据库发现LIFR上游miroRNA。结果LIFR在多种癌症中普遍下调,乳腺癌中LIFR与肿瘤突变负荷肿瘤突变符合、微卫星不稳定性呈负相关关系,且LIFR的表达含量与乳腺癌肿瘤微环境中的基质细胞含量具有正相关性。预后分析结果显示,乳腺癌中高表达LIFR能够显著改善患者总生存期、肿瘤无远处转移生存期、无复发生存期。进一步分析发现,乳腺癌中LIFR的表达水平在免疫亚型、乳腺癌分子亚型中差异不明显,不同组织类型、乳腺癌亚型、乳腺癌分期、不同组织学分类、不同年龄分期中均存在LIFR启动子甲基化现象,总体来说LIFR在乳腺癌中表现为低甲基化。细胞实验结果证实MDA-MB-231细胞中LIFR显著下调,过表达LIFR抑制乳腺癌细胞的迁移和侵袭且LIFR可与miR-27a结合。结论LIFR可以作为乳腺癌的免疫浸润和预后标志物。Objective Analyzing the effects of leukemia suppressor receptor(LIFR)on prognosis and tumor microenvironmental immune cell infiltration in breast cancer by bioinformatics analysis.Methods The expression of LIFR was analyzed by Oncomine database and TIMER.The relationship between LIFR and tumor mutational burden and microsatellite instability was investigated using data downloaded from UCSC Xena.The correlation between LIFR and tumor microenvironment of breast cancer was evaluated using the“ESTIMATE”R package.Prognostic scan and Kaplan-Meier plotter were used to evaluate the impact of LIFR on clinical prognosis of breast cancer.The TISIDB database was further used to evaluate the distribution of LIFR in different immune subtypes and molecular subtypes in breast cancer,and the UALCAN database was used to analyze the methylation of LIFR promoter in breast cancer.In addition,the expression of LIFR was confirmed by quantitative real-time PCR,and evaluating the migration of breast cancer cells through wound healing assay.Finally,predicating microRNAs/mRNA interaction using the miRTarBase,TargetScan,microRNA.org and miRDB software.Results LIFR was generally down-regulated in a variety of cancers,and the tumor mutational burden and microsatellite instability showed a negative correlation in breast cancer.Moreover,the expression of LIFR was positively correlated with the content of stromal cells in the microenvironment of breast cancer.High expression of LIFR was related to a better overall survival of breast cancer.In addition,LIFR was related to the relapse-free survival and distance metastasis free survival.Further analysis found that the expression level of LIFR in breast cancer was not significantly different among immune subtypes and breast cancer molecular subtypes,and methylation of the LIFR promoter existed in different tissue types,breast cancer subtypes,breast cancer stages,different histological classifications,and different age stages.In general,LIFR was hypomethylated in breast cancer.The cell experiment

关 键 词：乳腺癌 免疫 预后 生物信息学 

分 类 号：R73[医药卫生—肿瘤]