基于免疫相关miRNA-mRNA作用网络的乳腺癌预后模型建立  

A prognostic prediction model based on immune-related miRNA-mRNA network for breast cancer

作　　者：黄萍 唱凯 陈鸣 HUANG Ping;CHANG Kai;CHEN Ming(Department of Clinical Laboratory Medicine,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing 400038,China)

机构地区：[1]陆军军医大学第一附属医院检验科,重庆400038

出　　处：《免疫学杂志》2024年第12期906-912,共7页Immunological Journal

基　　金：国家自然科学基金(82030066,U23A2047)。

摘　　要：目的探讨基于免疫相关microRNA-mRNA作用网络(immune-related miRNA-mRNA network,IRM-MN)的风险回归模型用于评估乳腺癌(breast cancer,BC)组织免疫细胞浸润水平及患者预后的潜力。方法从TCGA数据库(The Cancer Genome Atlas)和GEO数据库(Gene Expression Omnibus DataSets)获取转录组数据与临床数据,通过差异分析、共表达分析和LASSO(Least Absolute Shrinkage and Selection Operator)回归分析筛选出差异表达的免疫相关miRNAs与mRNAs;通过COX回归分析筛选出与BC预后相关的、差异表达的免疫相关miRNAs与mRNAs并构建预后风险评分模型;使用Kaplan-Meier生存分析、ROC曲线、单/多因素独立预后分析和相关性分析评价模型的预测能力。结果共筛选出3个与预后相关的差异免疫相关miRNAs及5个与预后相关的差异免疫mRNAs,最终确定2个miRNAs(miR-21-5p和miR-141-3p)和1个mRNA(INHBA)用于构建风险模型。Kaplan-Meier生存分析表明高风险组BC患者预后较差(P<0.001)。ROC曲线结果显示,总体生存率曲线下面积(area under curve,AUC)值为0.893。单因素和多因素的独立预后分析结果显示,模型的风险评分可作为BC患者生存结局评估的独立预后因素(风险比:1.234,P<0.001)。此外,模型的风险评分与巨噬细胞免疫评分存在正相关性。结论本研究明确了与BC预后相关的特征性差异免疫相关miRNAs和mRNAs。基于IRM-MN作用网络构建的风险回归模型具有较高的预后预测及肿瘤免疫浸润评估价值。因此,该风险模型可为BC患者的预后评估及个性化治疗方案的改善提供可靠的参考。Objective To investigate the potential in a risk regression model based on an immune-related microRNA-mRNA network to evaluate immune cell infiltration and prognosis in breast cancer(BC).Methods Transcriptomic and clinical data were obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus DataSets(GEO)databases.Differential expressions of immune-related miRNAs and mRNAs were elaborated using differential and co-expression analysis and LASSO(Least Absolute Shrinkage and Selection Operator)regression analysis.COX regression analysis was used to select prognostic factors and construct risk regression.Kaplan-Meier survival analysis,ROC curve,univariate/multivariate independent prognostic analysis,and correlation analysis were used to evaluate the predictive value of this risk model.Results Three differential immune-related miRNAs and five differential immune mRNAs were considered as prognostic factors for BC.Finally,two miRNAs(miR-21-5p and miR-141-3p)and one mRNA(INHBA)were utilized to construct the risk regression model.Kaplan-Meier survival analysis showed that the high-risk group had a poor prognosis compared to the low-risk group(P<0.001).The receiver operating characteristic(ROC)curve showed that area value under curve(AUC)was 0.893.The univariate and multivariate independent prognostic analysis showed that risk score was an independent prognostic factor for BC(HR:1.234,P<0.001).Moreover,there was a positive correlation between the risk score and macrophage immune score.Conclusion This study identified characteristic differential immune-related miRNAs and mRNAs associated with BC prognosis.This risk regression model based on IRM-MN has predictive value in prognostic and tumor immune infiltration evaluation.Therefore,this model can satisfactorily evaluate the prognosis of BC patients and provide a reliable reference for individualized therapy.

关 键 词：乳腺癌 免疫相关miRNA-mRNA网络 预后 

分 类 号：R737.9[医药卫生—肿瘤] R392[医药卫生—临床医学]