基于生物信息学分析SPNS2对乳腺癌预后、诊断或免疫浸润的影响  

Effect of SPNS2 on prognosis,diagnosis or immune invasion of breast cancer based on bioinformatics

作　　者：李迪佳 王敏杰 马丽杰 李乐慧 闫涛 邬艺璇 牛燕[2] 白雪[2] 张楠 张子英 LI Dijia;WANG Minjie;MA Lijie;LI Lehui;YAN Tao;WU Yixuan;NIU Yan;BAI Xue;ZHANG Nan;ZHANG Ziying(Department of Pharmacology,Basic Medicine College of Inner Mongolia Medical University,Hohhot 010000,China;Medical Experiment Center of Inner Mongolia Medical University;Laboratory of Molecular Epidemiology of Chronic Diseases;Public Health College of Inner Mongolia Medical University)

机构地区：[1]内蒙古医科大学基础医学院药理学教研室,呼和浩特010000 [2]内蒙古医科大学医学实验中心 [3]慢性病分子流行病实验室 [4]内蒙古医科大学公共卫生学院

出　　处：《山西医科大学学报》2024年第4期455-465,共11页Journal of Shanxi Medical University

基　　金：内蒙古自治区自然科学基金项目(2020MS08136,2020BS08015,2023QN08030);内蒙古自治区卫健委医疗卫生科技计划项目(202202123,202202148);内蒙古医科大学校级面上项目(YKD2021MS044,YKD2022MS011,YKD2021MS008,YKD2022MS079);内蒙古医科大学博士启动基金项目(YKD2020BSJJ017);内蒙古自治区高等学校科学研究项目(NJZY22624,NJZY22645)。

摘　　要：目的应用生物信息学方法探讨鞘氨醇-1-磷酸转运体2(sphingosine-1-phosphate transporter 2,SPNS2)在乳腺癌中的表达情况,并分析SPNS2对乳腺癌预后、诊断或免疫浸润的影响。方法癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库检索乳腺癌组织和非乳腺癌样本中的SPNS2 mRNA差异表达数据,并分析SPNS2与乳腺癌之间的关系。用Cox单因素及多因素模型分析SPNS2 mRNA表达对乳腺癌预后的影响。使用Kaplan-Meier曲线评估SPNS2基因的表达与存活率之间的相关性,分析SPNS2对乳腺癌患者生存预后的影响。使用受试者工作特征曲线(receiver operating characteristic,ROC)分析SPNS2对乳腺癌的诊断效能。使用肿瘤免疫估算资源(Tumor Immune Estimation Resource,TIMER)数据库分析SPNS2表达与乳腺癌免疫微环境中不同类型免疫细胞的相关性。搜索相互作用基因检索的工具(Search Tool for the Retrieval of Interacting Genes,STRING)数据库分析乳腺癌中SPNS2与相关蛋白质之间的相互作用。分析京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库中得到的差异基因富集的信号通路。提取正常乳腺上皮细胞和乳腺癌细胞系RNA,通过RT-qPCR实验比较SPNS2的表达水平。结果在TCGA乳腺癌数据库中,SPNS2在乳腺癌组织中表达水平显著低于癌旁组织(P<0.001),SPNS2 mRNA的表达与T、M分期、病理分期、PAM50分型、年龄和组织学类型等因素相关(P<0.05);Cox分析表明年龄>60岁、T4期、M1期等因素是乳腺癌发生预后不良的风险因素(P<0.01);Kaplan-Meier分析显示低表达SPNS2乳腺癌患者具有更长的疾病特异生存期(disease-specific survival,DSS)和无进展间隔期(progression-free interval,PFI)(P<0.05);ROC曲线提示SPNS2诊断具有较好的敏感性和特异性。TIMER数据库分析显示在Luminal型乳腺癌中,SPNS2与CD4+T细胞,巨噬细胞、中性粒细胞等免疫细胞呈正相关(P<0.05)。STRING和KEGG数据�Objective To explore the expression of sphingosine-1-phosphate transporter 2(SPNS2)in breast cancer tissues and analyze the relationship between SPNS2 and breast cancer immune infiltration and patient prognosis using a bioinformatic approach.Methods The Cancer Genome Atlas(TCGA)was used to retrieve data on the difference in mRNA expression of SPNS2 in breast cancer and normal breast tissues and analyze the relationship between SPNS2 and breast cancer.Cox univariate and multifactorial models were used to analyze the effect of SPNS2 mRNA expression on the prognosis of breast cancer patients.Kaplan-Meier Plotter curves were utilized to evaluate the correlation between SPNS2 gene expression and survival and analyze the effect of SPNS2 on survival of breast cancer patients.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic efficacy of SPNS2 for breast cancer.The Tumor Immune Estimation Resource(TIMER)database was used to analyze the correlation between SPNS2 expression and different types of immune cells in the immune microenvironment of breast cancer.The Search Tool for the Retrieval of Interacting Genes(STRING)database was used to explore the interaction between SPNS2 and related proteins in breast cancer.The Kyoto Encyclopedia of Genes and Genomes(KEGG)database was used to analyze the signaling pathways of the differential genes.RNA was extracted from normal breast epithelial cells and breast cancer cell lines,and the expression level of SPNS2 was detected by RT-qPCR assay.Results In the TCGA breast cancer database,the expression level of SPNS2 in breast cancer tissues was significantly lower than that in adjacent tissues(P<0.001).The expression of SPNS2 mRNA was correlated with T,M stage,pathological stage,PAM50 type,age and histological type(P<0.05).Cox analysis showed that age>60 years,T4 stage,M1 stage and other factors were the risk factors for the poor prognosis of breast cancer(P<0.01).Kaplan-Meier analysis showed that breast cancer patients with low expression of SPNS2 had long

关 键 词：鞘氨醇-1-磷酸转运体2(SPNS2) 乳腺癌 免疫浸润 预后 生物信息学 

分 类 号：R737.9[医药卫生—肿瘤]