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越来越多的证据表明，微核糖核酸（miRNA）对于乳腺癌的结局预测具有重要作用。 2019年9月23日，美国纽约奥尔巴尼《老龄化》在线发表广东省人民医院广东省医学科学院、中山大学孙逸仙纪念医院的研究报告，探讨了乳腺癌复发相关miRNA，并且建立了新的患者风险精准分层系统。 该研究通过分析比较美国国家癌症研究所癌症基因组图谱（TCGA）数据库1044例乳腺癌组织和102例相邻正常组织标本，确认了共计381个表达不同的miRNA。 随后，根据每个miRNA与无病生存之间的相关性，确定与复发相关的miRNA谱，利用多因素比例风险回归模型构建了新的预后列线图，通过美国基因本体数据库和日本京都大学基因与基因组百科全书（KEGG）人类基因组数据库，对4个miRNA的46个靶基因进行分析。 根据预测5年无病生存的特异度与灵敏度曲线分析，miRNA谱＋TNM分期（肿瘤原发灶、区域淋巴结、远处转移灶）与单纯TNM分期相比，曲线下面积显著较高（0.710比0.616，P<0.0001）。 此外，风险分层分析表明，根据miRNA谱建立的预后模型，可以将897例演算队列和449例验算队列的患者，分为显著高风险和显著低风险两组（全部P<0.0001），无论其他临床特征如何。 根据基因组功能富集分析，与对照基因组分布特征相比，46个靶基因在统计意义上显著相关的生物学功能和信号转导通路，主要集中于重要的细胞生物学过程、蛋白质结合和癌症相关信号转导通路。 因此，该研究结果表明，根据miRNA谱建立的预后模型可能有助于乳腺癌患者个体化治疗决策。 Aging (Albany NY). 2019 Sep 23;11. [Epub ahead of print] Identification of a novel microRNA recurrence-related signature and risk stratification system in breast cancer. Lai J, Chen B, Zhang G, Wang Y, Mok H, Wen L, Pan Z, Su F, Liao N. Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 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. KEYWORDS: breast cancer; microRNA; model; recurrence; survival PMID: 31548433 DOI: 10.18632/aging.102268
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