Circulating microRNA-203 predicts metastases, early recurrence, and poor prognosis in human gastric cancer
Circulating microRNA-203 predicts metastases, early recurrence, and poor prognosis in human gastric cancer
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DOI：
10.1007/s10120-015-0521-0
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发表时间：
2016-07-01
期刊：
影响因子：
7.4
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
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作者：
Imaoka, Hiroki;Toiyama, Yuji;Kusunoki, Masato
转移是胃癌患者死亡的主要原因。与上皮-间充质转化(EMT)相关的microRNAs(MiRNAs)控制着胃癌的进展和转移。在本研究的第一步(初步实验)中，我们通过分析miR-200家族(miR-200a、miR-200b、miR-200c、miR-141和miR-429)和miR-203在I期(n=12)和IV期(n=12)胃癌患者血清中的表达，筛选出与转移相关的候选miRNAs。第二阶段是对130例胃癌患者和22例正常对照血清标本中的miRNAs进行独立验证，在初步实验的基础上，选择miR-203作为与肿瘤转移关系最密切的候选血清miRNA。验证分析显示，IV期患者的血清miR-203水平显著低于I-III期GC患者。血清miR-203的表达在T分期、血管侵犯、淋巴结、腹膜和远处转移较高的GC患者中显著降低。血清miR-203的低表达与较差的无病生存率和总体生存率显著相关。多因素分析显示，血清miR-203低表达是胃癌患者淋巴结、腹膜和远处转移的独立预测指标，且预后不良。血清miR-203可作为预测胃癌患者预后和转移的无创性生物标志物。
Metastasis is a major cause of death in patients with gastric cancer (GC). MicroRNAs (miRNAs) relating to the epithelial-mesenchymal transition (EMT) control GC progression and metastasis. The aim of this study was to evaluate serum EMT-associated miRNAs for metastatic and prognostic noninvasive biomarkers in GC.In the first step of this study (preliminary experiments), we selected candidate miRNAs associated with metastasis by analyzing the expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and miR-203 in serum samples from stage I (n = 12) and stage IV (n = 12) GC patients. The second phase involved the independent validation of candidate miRNAs in serum specimens from 130 patients with GC and 22 controls.Based on the preliminary experiments, miR-203 was selected as the candidate serum miRNA that was most closely associated with metastasis. Validation analysis revealed that serum miR-203 levels were significantly lower in stage IV than stage I-III GC patients. Serum miR-203 expression was significantly lower in GC patients with a higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases. Low expression of serum miR-203 was significantly associated with poor disease-free and overall survival. Multivariate analysis revealed that low serum miR-203 expression was an independent predictive marker for lymph node, peritoneal, and distant metastases and a poor prognosis in patients with GC.Serum miR-203 has the potential to serve as a noninvasive biomarker for prognosis and to predict metastasis in patients with GC.