Circulating miR-17-5p and miR-20a: Molecular markers for gastric cancer
Circulating miR-17-5p and miR-20a: Molecular markers for gastric cancer
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循环 miR-17-5p 和 miR-20a：胃癌的分子标志物
DOI：
10.3892/mmr.2012.828
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发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
Xu, Wenrong
中科院分区：
文献类型：
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作者：
Wang, Mei;Gu, Hongbing;Xu, Wenrong
已证明胃癌患者血浆中的循环 miR-17-5p 和 miR-20a (miR-17-5p/20a) 升高。然而，这些 microRNA (miRNA) 循环水平的临床意义、预后预测能力以及监测化疗效果的应用仍不清楚。为此，我们测量了未配对的术前 (n=65)、术后 (n=16) 和复发 (n=6) 胃癌患者组的血浆 miR-17-5p/20a 水平。记录未配对的术前患者的3年总生存率。还在 14 名胃癌患者的配对术前和术后血浆中测试了 miR-17-5p/20a 的循环水平。我们发现miR-17-5p/20a的浓度与胃癌的分化状态和TNM分期显着相关。不同组中的miRNA水平反映了肿瘤的病理进展。 Kaplan-Meier 曲线分析显示，miR-17-5p/20a 的高表达水平与较差的总生存率显着相关。 Cox回归分析表明血浆miR-20a水平是预后的独立风险预测因子。建立体内小鼠肿瘤模型，并应用针对miR-17-5p/20a的antagomir作为化疗药物进行肿瘤治疗。血清 miR-17-5p/20a 水平测定显示，治疗后肿瘤体积消退的小鼠血清 miRNA 水平显着降低。综上所述，循环 miR-17-5p/20a 的水平可能是一种有前途的非侵入性分子标志物，用于胃癌的病理进展、预后预测和化疗效果监测。
Circulating miR-17-5p and miR-20a (miR-17-5p/20a) have been demonstrated to be elevated in the plasma of gastric cancer patients. However, the,clinical significance of the circulating levels of these microRNAs (miRNAs), the predictive power for prognosis and application for monitoring of chemotherapeutic effects remain unclear. To this end, we measured plasma miR-17-5p/20a levels in unpaired pre-operative (n=65), post-operative (n=16) and relapse (n=6) gastric cancer patient groups. The 3-year overall survival rate for the unpaired pre-operative patients was recorded. The circulating levels of miR-17-5p/20a were also tested in paired pre-operative and post-operative plasma from 14 gastric cancer patients. We found that the concentrations of miR-17-5p/20a were significantly associated with the differentiation status and TNM stages of gastric cancer. The miRNA levels in the different groups reflected pathological tumor progression. Kaplan-Meier curve analysis revealed that high expression levels of miR-17-5p/20a were significantly correlated with poor overall survival. Cox regression analysis demonstrated that the level of plasma miR-20a was an independent risk predictor for prognosis. An in vivo mouse tumor model was established and antagomirs against miR-17-5p/20a were applied as chemotherapeutics to perform tumor treatment. An assay of serum miR-17-5p/20a levels showed that the levels of serum miRNAs were notably reduced in post-treated mice with tumor volume regression. Taken together, the levels of circulating miR-17-5p/20a may be a promising non-invasive molecular marker for pathological progression, prediction of prognosis and monitoring of chemotherapeutic effects for gastric cancer.