Department of Digestive Diseases, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei, China.
PLoS One. 2012;7(7):e40037. doi: 10.1371/journal.pone.0040037. Epub 2012 Jul 3.
Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients.
A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR.
We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-β, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion.
Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.
胃癌（GC）是中国癌症患者中最常见的恶性肿瘤和主要死亡原因之一。复发是导致 GC 患者手术后治疗失败和 5 年生存率降低的主要因素。因此，寻找具有预测复发风险潜力的生物标志物是 GC 患者预后的关键问题。
共对 74 例 GC 患者进行系统分析，其中 31 例患者复发，43 例患者无复发。首先，采用 miRNA 微阵列和生物信息学方法从原发肿瘤样本中描述差异表达的 miRNA。然后，我们使用 ROC 方法选择具有最佳灵敏度和特异性的特征。最后，使用定量 PCR 法在 GC 样本（新鲜冰冻和血液样本）中验证该特征。
我们发现了 12 个差异表达的 miRNA，包括 7 个上调和 5 个下调的 miRNA 在复发组中。使用 ROC 方法，我们进一步确定 hsa-miR-335 为识别训练样本中复发和非复发病例的特征。此外，我们使用定量 PCR 法在 64 个测试样本中验证了该特征，结果与训练集一致。在 hsa-miR-335 水平较高的 GC 病例中，观察到高复发频率和不良生存（P<0.001）。此外，我们评估了 hsa-miR-335 参与调节多个致癌信号通路中的靶基因，如 p53、MAPK、TGF-β、Wnt、ERbB、mTOR、Toll 样受体和粘着斑。
我们的结果表明，hsa-miR-335 具有识别复发风险的潜力，并与 GC 患者的预后相关。
