Lai Jianguo, Chen Bo, Zhang Guochun, Wang Yulei, Mok Hsiaopei, Wen Lingzhu, Pan Zihao, Su Fengxi, Liao Ning
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Aging (Albany NY). 2019 Sep 23;11(18):7525-7536. doi: 10.18632/aging.102268.
Increasing evidence has revealed that microRNAs (miRNAs) play vital roles in breast cancer (BC) prognosis. Thus, we aimed to identify recurrence-related miRNAs and establish accurate risk stratification system in BC patients. A total of 381 differentially expressed miRNAs were confirmed by analyzing 1044 BC tissues and 102 adjacent normal samples from The Cancer Genome Atlas (TCGA). Then, based on the association between each miRNAs and disease-free survival (DFS), we identified miRNA recurrence-related signature to construct a novel prognostic nomogram using Cox regression model. Target genes of the four miRNAs were analyzed via Gene Ontology and KEGG pathway analyses. Time-dependent receiver operating characteristic analysis indicated that a combination of the miRNA signature and tumor-node-metastasis (TNM) stage had better predictive performance than that of TNM stage (0.710 vs 0.616, <0.0001). Furthermore, risk stratification analysis suggested that the miRNA-based model could significantly classify patients into the high- and low-risk groups in the two cohorts (all <0.0001), and was independent of other clinical features. Functional enrichment analysis demonstrated that the 46 target genes mainly enrichment in important cell biological processes, protein binding and cancer-related pathways. The miRNA-based prognostic model may facilitate individualized treatment decisions for BC patients.
越来越多的证据表明,微小RNA(miRNA)在乳腺癌(BC)预后中起着至关重要的作用。因此,我们旨在识别与复发相关的miRNA,并在BC患者中建立准确的风险分层系统。通过分析来自癌症基因组图谱(TCGA)的1044例BC组织和102例相邻正常样本,共确认了381个差异表达的miRNA。然后,基于每个miRNA与无病生存期(DFS)之间的关联,我们识别出与miRNA复发相关的特征,使用Cox回归模型构建了一种新的预后列线图。通过基因本体论和KEGG通路分析对这四种miRNA的靶基因进行了分析。时间依赖性受试者工作特征分析表明,miRNA特征与肿瘤-淋巴结-转移(TNM)分期相结合的预测性能优于TNM分期(0.710对0.616,<0.0001)。此外,风险分层分析表明,基于miRNA的模型可以在两个队列中将患者显著分为高风险和低风险组(均<0.0001),并且独立于其他临床特征。功能富集分析表明,46个靶基因主要富集在重要的细胞生物学过程、蛋白质结合和癌症相关通路中。基于miRNA的预后模型可能有助于BC患者的个体化治疗决策。