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基于 TCGA 数据的胰腺腺癌生存预后的五 miRNA -signature。

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

机构信息

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Sci Rep. 2018 May 16;8(1):7638. doi: 10.1038/s41598-018-22493-5.

Abstract

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.

摘要

由于胰腺腺癌预后较差,因此迫切需要新的生物标志物。在这里,我们通过使用癌症基因组图谱 (TCGA) RNA-seq 数据,评估了差异表达 miRNA 的预后价值,并构建了一个能够有效预测患者总生存期 (OS) 的五 miRNA 特征。基于这五个 miRNA 的两组 Kaplan-Meier 总生存曲线明显不同,高危组和低危组患者的五年总生存率分别为 10.2%和 47.8%。ROC 曲线分析的 AUC 为 0.775,表明五 miRNA 特征模型在预测胰腺腺癌患者生存风险方面具有良好的敏感性和特异性。功能富集分析表明,miRNA 特征的靶基因可能参与与癌症相关的各种途径,包括 PI3K-Akt、TGF-β 和多能干细胞信号通路。最后,我们分析了 miRNA 特征中五个特定 miRNA 的表达,并在 20 名新诊断的胰腺腺癌患者中使用 qRT-PCR 验证了结果的可靠性。qRT-PCR 的表达结果与 TCGA 的结果一致。总之,这些发现表明,五 miRNA 特征 (hsa-miR-203、hsa-miR-424、hsa-miR-1266、hsa-miR-1293 和 hsa-miR-4772) 可用作胰腺腺癌的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5d/5955976/cd77efe3936c/41598_2018_22493_Fig1_HTML.jpg

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