A Five-microRNA Signature for Survival Prognosis in Pancreatic Adenocarcinoma based on TCGA Data.

A Five-microRNA Signature for Survival Prognosis in Pancreatic Adenocarcinoma based on TCGA Data.
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基于 TCGA 数据的胰腺腺癌生存预测的五种 microRNA 特征

DOI:
10.1038/s41598-018-22493-5
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发表时间:
2018-05-16
期刊:
影响因子:
4.6
通讯作者:
Qin RY
Qin RY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shi XH;Li X;Zhang H;He RZ;Zhao Y;Zhou M;Pan ST;Zhao CL;Feng YC;Wang M;Guo XJ;Qin RY

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胰腺癌预后差,迫切需要新的生物标志物。在这里,通过使用癌症基因组图谱(TCGA)RNA-seq数据,我们评估了差异表达的miRNA的预后价值,并构建了一个可以有效预测患者总生存期(OS)的五个miRNA签名。基于5种miRNAs的两组Kaplan-Meier总生存曲线有显著差异,高风险组和低风险组患者的5年总生存率分别为10.2%和47.8%。ROC曲线分析的AUC为0.775,显示了5-miRNA签名模型在预测胰腺癌患者生存风险方面具有良好的灵敏度和特异性。功能富集分析表明,miRNA标签的靶基因可能参与与癌症相关的多种途径,包括PI 3 K-Akt、TGF-β和多能干细胞信号传导途径。最后,我们分析了miRNA签名中的五种特异性miRNA的表达,并使用qRT-PCR验证了20例新诊断胰腺癌患者结果的可靠性。qRT-PCR的表达结果与TCGA结果一致。综上所述,这些发现表明,五种miRNA特征(hsa-miR-203、hsa-miR-424、hsa-miR-1266、hsa-miR-1293和hsa-miR-4772)可用作胰腺癌的预后标志物。
Novel biomarkers for pancreatic adenocarcinoma are urgently needed because of its poor prognosis. Here, by using The Cancer Genome Atlas (TCGA) RNA-seq data, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a five-miRNA signature that could effectively predict patient overall survival (OS). The Kaplan-Meier overall survival curves of two groups based on the five miRNAs were notably different, showing overall survival in 10.2% and 47.8% at five years for patients in high-risk and low-risk groups, respectively. The ROC curve analysis achieved AUC of 0.775, showing good sensitivity and specificity of the five-miRNA signature model in predicting pancreatic adenocarcinoma patient survival risk. The functional enrichment analysis suggested that the target genes of the miRNA signature may be involved in various pathways related to cancer, including PI3K-Akt, TGF-β, and pluripotent stem cell signaling pathways. Finally, we analyzed expression of the five specific miRNAs in the miRNA signature, and validated the reliability of the results in 20 newly diagnosed pancreatic adenocarcinoma patients using qRT-PCR. The expression results of qRT-PCR were consistent with the TCGA results. Taken together, these findings suggested that the five-miRNA signature (hsa-miR-203, hsa-miR-424, hsa-miR-1266 hsa-miR-1293, and hsa-miR-4772) could be used as a prognostic marker for pancreatic adenocarcinoma.
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