Identification of circulating microRNA signatures as potential noninvasive biomarkers for prediction and prognosis of lymph node metastasis in gastric cancer.

Identification of circulating microRNA signatures as potential noninvasive biomarkers for prediction and prognosis of lymph node metastasis in gastric cancer.
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鉴定循环 microRNA 特征作为胃癌淋巴结转移预测和预后的潜在非侵入性生物标志物

DOI:
10.18632/oncotarget.17789
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发表时间:
2017-09-12
期刊:
影响因子:
--
通讯作者:
Wang C
Wang C
中科院分区:
其他
文献类型:
--
作者:
Jiang X;Wang W;Yang Y;Du L;Yang X;Wang L;Zheng G;Duan W;Wang R;Zhang X;Wang L;Chen X;Wang C

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循环microRNA(microRNAs,miRNAs)是一种新的预测肿瘤淋巴结转移的非侵袭性生物标志物。本研究的目的是鉴定血清miRNA特征用于预测和预后胃癌(GC)中LNM。进行MiSeq测序以在10名具有LNM的GC患者、10名没有LNM的患者和10名健康对照中初步筛选血清miRNA。应用逆转录定量实时PCR以使用训练群组(n = 279)和验证群组(n = 180)确认候选miRNA的浓度。我们通过多变量逻辑回归模型鉴定了一组四种miRNA(miR-501- 3 p、miR-143- 3 p、miR-451 a、miR-146 a),该模型在训练集中提供了对LNM的高预测准确性,其受试者工作特征曲线下面积(AUC)为0.891(95%CI,0.840至0.930)。对该组的前瞻性评价显示,验证集中的AUC为0.822(95% CI,0.758 - 0.875,特异性= 87.78%,灵敏度= 63.33%)。此外,Kaplan-Meier分析显示,低miR-451 a和miR-146 a水平的LNM患者的总生存期(OS)较差(p < 0.05)。在考克斯回归分析中,miR-451 a与LNM的OS独立相关(p = 0.028)。我们的研究结果表明,使用血清miRNAs似乎有希望在估计的可能性GC患者的港口LNM和提供预后信息的LNM。
Circulating microRNAs (miRNAs) are emerging as novel noninvasive biomarkers for prediction of lymph node metastasis (LNM) in cancer. The aim of this study was to identify serum miRNA signatures for prediction and prognosis of LNM in gastric cancer (GC). MiSeq sequencing was performed for an initial screening of serum miRNAs in 10 GC patients with LNM, 10 patients without LNM and 10 healthy controls. Reverse transcription quantitative real-time PCR was applied to confirm concentration of candidate miRNAs using a training cohort (n = 279) and a validation cohort (n = 180). We identified a four-miRNA panel (miR-501-3p, miR-143-3p, miR-451a, miR-146a) by multivariate logistic regression model that provided high predictive accuracy for LNM with an area under the receiver operating characteristic curve (AUC) of 0.891 (95% CI, 0.840 to 0.930) in training set. Prospective evaluation of this panel revealed an AUC of 0.822 (95% CI, 0.758 to 0.875, specificity = 87.78%, sensitivity = 63.33%) in validation set. Moreover, Kaplan–Meier analysis showed that LNM patients with low miR-451a and miR-146a levels had worse overall survival (OS) (p < 0.05). In Cox regression analysis, miR-451a was independently associated with OS of LNM (p = 0.028). Our results suggested that use of serum miRNAs seems promising in estimating the probability GC patients harbor LNM and providing prognostic information for LNM.
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