Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma.

Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma.
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血清 miRNA 表达谱作为 II/III 期结直肠腺癌的预后生物标志物

DOI:
10.1038/srep12921
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发表时间:
2015-08-07
期刊:
影响因子:
4.6
通讯作者:
Ba Y
Ba Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li J;Liu Y;Wang C;Deng T;Liang H;Wang Y;Huang D;Fan Q;Wang X;Ning T;Liu R;Zhang CY;Zen K;Chen X;Ba Y

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我们试图确定血清miRNA表达谱,以改善疾病监测和预测II/III期结直肠癌(CRC)患者术后疾病复发。使用TaqMan低密度阵列(TLDA),我们进行了初步调查,以分析20对术前和术后CRC患者和20名匹配的正常受试者的合并血清中的749个miRNA。在175例II/III期CRC患者中使用个体RT-qPCR验证,我们确定了miR-145、miR-106 a和miR-17- 3 p在术前和术后CRC患者之间以及术前CRC患者和正常对照之间的显著差异表达(P< 0.0001)。用于区分术前CRC患者和正常受试者的三种miRNA组的ROC曲线下面积(AUC)为0.886(95%CI 0.850-0.921),用于区分术前和术后CRC患者的ROC曲线下面积(AUC)为0.850(95%CI 0.809-0.891)。此外,使用Kaplan-Meier方法和考克斯比例风险分析,我们发现miR-17- 3 p和miR-106 a是强有力的独立预后指标,高水平的这些miRNA与较短的无病生存期(DFS)相关(miR-17- 3 p P< 0.0001,miR-106 a P = 0.001)。本研究揭示了新的基于血清miRNA的生物标志物,用于监测肿瘤动力学以及预测II/III期CRC患者的疾病复发。
We sought to identify a serum miRNA expression profile to improve disease surveillance and to predict post-operative disease recurrence for stage II/III colorectal cancer (CRC) patients. Using the TaqMan Low-Density Array (TLDA), we performed an initial survey to analyze 749 miRNAs in the pooled serum of 20 paired pre- and post-operative CRC patients and 20 matched normal subjects. Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P< 0.0001). The area under the ROC curve (AUC) for the three-miRNA panel was 0.886 (95% CI 0.850–0.921) for discriminating between pre-operative CRC patients and normal subjects and 0.850 (95% CI 0.809–0.891) for discriminating between pre- and post-operative CRC patients. Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P< 0.0001 for miR-17-3p andP= 0.001 for miR-106a). The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.