Identification of a novel microRNA recurrence-related signature and risk stratification system in breast cancer
Identification of a novel microRNA recurrence-related signature and risk stratification system in breast cancer
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乳腺癌中新型 microRNA 复发相关特征和风险分层系统的鉴定
DOI：
10.18632/aging.102268
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发表时间：
2019-09-30
期刊：
影响因子：
5.2
通讯作者：
Liao, Ning
中科院分区：
文献类型：
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作者：
Lai, Jianguo;Chen, Bo;Liao, Ning
越来越多的证据表明microRNAs（miRNAs）在乳腺癌预后中起着重要作用。因此，我们的目的是确定复发相关的miRNA，并建立准确的风险分层系统在BC患者。通过分析来自癌症基因组图谱（TCGA）的1044个BC组织和102个相邻正常样品，总共确认了381个差异表达的miRNA。然后，基于各miRNA与无病生存期（DFS）之间的相关性，我们利用考克斯回归模型识别了与miRNA复发相关的特征，构建了一个新的预后诺模图。通过Gene Ontology和KEGG途径分析四种miRNAs的靶基因。时间依赖的受试者工作特征分析表明，miRNA标签与肿瘤淋巴结转移（TNM）分期相结合的预测效能优于TNM分期（0.710 vs 0.616，P<0.0001）。此外，风险分层分析表明，基于miRNA的模型可以将两个队列中的患者显著分类为高风险组和低风险组（均P<0.0001），并且与其他临床特征无关。功能富集分析表明，这46个靶基因主要富集在重要的细胞生物学过程、蛋白结合和肿瘤相关通路中。基于miRNA的预后模型可能有助于BC患者的个体化治疗决策。
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, P<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 P<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.