Department of Gastrointestinal Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing.
Ann Oncol. 2011 Oct;22(10):2257-66. doi: 10.1093/annonc/mdq758. Epub 2011 Feb 22.
Recurrence is a major factor leading to treatment failure and death in gastric cancer (GC) patients following surgical resection. Importantly, the prediction of recurrence is critical in improving clinical outcomes. We isolated a group of microRNAs (miRNAs) and evaluated their usefulness as prognostic markers for the recurrence of GC.
A total of 65 GC patients were selected for systematic analysis, 29 patients with recurrence and 36 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize classifiers from primary tumor samples (n = 8). Following, we validated these predictors both in frozen fresh and paraffin-embedded tissue samples (n = 57) using quantitative PCR.
We have identified 17 differential miRNAs including 10 up-regulated and 7 down-regulated miRNAs in recurrence group. Using k-top scoring pairs (k-TSP) method, we further ascertained hsa-miR-375 and hsa-miR-142-5p as a classifier to recognize recurrence and nonrecurrence cases both in the training and test samples. Moreover, we validated this classifier in 34 frozen fresh tissues and 38 paraffin-embedded tissues with consistent sensitivity and specificity with training set; among them, 15 cases were matched. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-375 and low level of hsa-miR-142-5p (P < 0.001). In addition, we evaluated that hsa-miR-375 and hsa-miR-142-5p were involved in regulating target genes in several oncogenic signal pathways, such as TP53, MAPK, Wnt and vascular endothelial growth factor.
Our results indicate that the combination of hsa-miR-375 and hsa-miR-142-5p as a predictor of disease progression has the potential to predict recurrence risk for GC patients.
胃癌（GC）患者手术后复发是导致治疗失败和死亡的主要因素。重要的是，预测复发对于改善临床结局至关重要。我们分离了一组 microRNAs（miRNAs），并评估了它们作为 GC 复发预后标志物的有用性。
共选择了 65 例 GC 患者进行系统分析，其中 29 例有复发，36 例无复发。首先，使用 miRNA 微阵列和生物信息学方法从原发性肿瘤样本（n = 8）中对分类器进行特征描述。然后，我们使用定量 PCR 在冷冻新鲜和石蜡包埋组织样本（n = 57）中验证了这些预测因子。
我们发现 17 个差异表达的 miRNA，其中包括 10 个上调和 7 个下调的 miRNA 在复发组中。使用 k-最优得分对（k-TSP）方法，我们进一步确定 hsa-miR-375 和 hsa-miR-142-5p 作为一个分类器，能够在训练和测试样本中识别复发和非复发病例。此外，我们在 34 例冷冻新鲜组织和 38 例石蜡包埋组织中验证了该分类器，在训练集中具有一致的敏感性和特异性；其中 15 例匹配。在 hsa-miR-375 水平高和 hsa-miR-142-5p 水平低的 GC 病例中，观察到高复发率和不良生存率（P < 0.001）。此外，我们评估了 hsa-miR-375 和 hsa-miR-142-5p 参与调节几个致癌信号通路中的靶基因，如 TP53、MAPK、Wnt 和血管内皮生长因子。
我们的结果表明，hsa-miR-375 和 hsa-miR-142-5p 的组合作为疾病进展的预测因子，有可能预测 GC 患者的复发风险。
