首页|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

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

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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 Ency-clopedia 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数据库分析表明SPNS2相关蛋白富集于细胞周期和PPAR信号传导等途径(P＜0.05).RT-qPCR实验结果显示与正常乳腺上皮细胞相比,SPNS2在乳腺癌细胞系中低表达(P＜0.001).结论 SPNS2是一种潜在的诊断乳腺癌和评价预后的生物学标志物.
Effect of SPNS2 on prognosis,diagnosis or immune invasion of breast cancer based on bioinformatics
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 adja-cent 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,Ml 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 longer disease-specific survival and progression-free interval(P＜0.05).ROC curve indicated that SPNS2 had good sensitivity and specificity for breast cancer.TIMER database analysis showed that SPNS2 was positively correlated with CD4+T cells,macrophages,neutrophils and other immune cells in Luminal breast cancer(P＜0.05).STRING and KEGG database analysis showed that SPNS2 related proteins were enriched in cell cycle and PPAR signaling pathways(P＜0.05).The RT-qPCR results showed that SPNS2 expression was lower in breast cancer cell lines than in normal breast epithelial cells(P＜0.001).Conclusion SPNS2 is a potential biomarker for the diagnosis and prognosis of breast cancer.

sphingosine-1-phosphate transporter 2(SPNS2)breast cancerimmune infiltrationprognosisbioinformatics

李迪佳、王敏杰、马丽杰、李乐慧、闫涛、邬艺璇、牛燕、白雪、张楠、张子英

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内蒙古医科大学基础医学院药理学教研室,呼和浩特 010000

内蒙古医科大学医学实验中心

内蒙古医科大学慢性病分子流行病实验室

内蒙古医科大学公共卫生学院

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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

内蒙古自治区自然科学基金内蒙古自治区自然科学基金内蒙古自治区自然科学基金内蒙古自治区卫生健康委医疗卫生科技计划内蒙古自治区卫生健康委医疗卫生科技计划内蒙古医科大学校级面上项目内蒙古医科大学校级面上项目内蒙古医科大学校级面上项目内蒙古医科大学校级面上项目内蒙古医科大学博士启动基金内蒙古自治区高等学校科研项目内蒙古自治区高等学校科研项目

2020MS081362020BS080152023QN08030202202123202202148YKD2021MS044YKD2022MS011YKD2021MS008YKD2022MS079YKD2020BSJJ017NJZY22624NJZY22645

2024

10.13753/j.issn.1007-6611.2024.04.008

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子：0.931
ISSN：1007-6611
年,卷(期)：2024.55(4)
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