Fudan University Zhongshan Hospital, Shanghai, People's Republic of China.
Harvard T. H. Chan School of Public Health, Boston, MA.
Int J Cancer. 2017 Nov 15;141(10):2093-2102. doi: 10.1002/ijc.30895. Epub 2017 Jul 28.
Our aim was to identify plasma microRNA (miRNA)-based signatures to predict 3-year postoperative recurrence risk for patients with stage II and III gastric cancer (GC), so as to provide insights for individualized adjuvant therapy. Plasma miRNA expression was investigated in three phases, involving 407 patients recruited from three centers. ABI miRNA microarray and TaqMan Low Density Array were adopted in the discovery phase to identify potential miRNAs. Quantitative reverse-transcriptase polymerase chain reaction was used to assess the expression of selected miRNAs. Logistic regression models were constructed in the training set (n = 170) and validated in the validation set (n = 169). Receiver operating characteristic analyses, survival analyses and subgroup analyses were further used to assess the accuracy of the models. We identified a 7 miRNA classifier and 7miR + pathological factors index that provided high predictive accuracy of GC recurrence (area under the curve = 0.725 and 0.841 in the training set; and 0.627 and 0.771 in the validation set). High-risk patients defined by the signatures had significantly shorter disease-free survival and overall survival than low-risk patients. The 7 miRNA classifier is an independent prognostic factor, and could add predictive value to traditional prognostic factors. Subgroup analyses revealed the satisfactory performance persisted regardless of stage, and the two models both displayed high accuracy in stage IIA patients. In conclusion, identified microRNA signature may potentially provide some additional benefit for prediction of disease recurrence in patients with stage II and III GC.
我们的目的是确定基于血浆 microRNA(miRNA)的特征,以预测 II 期和 III 期胃癌(GC)患者的 3 年术后复发风险,从而为个体化辅助治疗提供见解。在三个阶段研究了血浆 miRNA 的表达,涉及三个中心招募的 407 名患者。在发现阶段采用 ABI miRNA 微阵列和 TaqMan 低密度阵列来识别潜在的 miRNAs。采用定量逆转录聚合酶链反应评估选定 miRNAs 的表达。在训练集(n = 170)中构建逻辑回归模型,并在验证集(n = 169)中进行验证。进一步使用受试者工作特征分析、生存分析和亚组分析来评估模型的准确性。我们确定了一个 7 miRNA 分类器和 7miR+病理因素指数,它们为 GC 复发提供了较高的预测准确性(在训练集中的曲线下面积为 0.725 和 0.841;在验证集中为 0.627 和 0.771)。根据签名定义的高危患者无病生存和总生存明显短于低危患者。7 miRNA 分类器是一个独立的预后因素,可以为传统的预后因素增加预测价值。亚组分析表明,无论分期如何,性能均令人满意,两个模型在 IIA 期患者中均显示出较高的准确性。总之,确定的 miRNA 特征可能为预测 II 期和 III 期 GC 患者的疾病复发提供一些额外的益处。