Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
Department of Anatomy, Luohe Medical College, Luohe, Henan, China.
J Cell Biochem. 2019 Oct;120(10):16416-16426. doi: 10.1002/jcb.28601. Epub 2019 Jul 11.
An microRNA (miRNA) signature to predict the clinical outcome of pancreatic adenocarcinoma (PAAD) is still lacking. In the current study, we aimed at identifying and evaluating a prognostic miRNA signature for patients with PAAD. The miRNA expression profile and the clinical information regarding patients with PAAD were recruited from The Cancer Genome Atlas database. Differentially expressed miRNAs were identified between normal and tumor samples. By means of survival analysis, a 4-miRNA signature for predicting patients' with PAAD overall survival (OS) was constructed. Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of survival prediction. Furthermore, the biological function of the predicted miRNAs was evaluated using a bioinformatics approach. Four (hsa-mir-126, hsa-mir-3613, hsa-mir-424, and hsa-mir-4772) out of 17 differentially expressed miRNAs were associated to the OS of patients with PAAD. Moreover, the area under the curve (AUC) of the constructed 4-miRNA signature associated to patients' with PAAD 2-year survival was 0.789. The multivariate Cox's proportional hazards regression model suggested that this 4-miRNA signature was an independent prognostic factor of other clinical parameters in patients with PAAD. Further pathway enrichment analyses revealed that the miRNAs in the 4-miRNA signature might regulate genes that affect focal adhesion, Wnt signaling pathway, and PI3K-Akt signaling pathway. Thus, these findings indicated that the 4-miRNA signature might be an effective independent prognostic biomarker in the prediction of PAAD patients' survival.
一种用于预测胰腺导管腺癌 (PAAD) 临床结局的 microRNA (miRNA) 特征仍然缺乏。在本研究中，我们旨在鉴定和评估用于 PAAD 患者的预后 miRNA 特征。从癌症基因组图谱 (TCGA) 数据库中招募了 miRNA 表达谱和 PAAD 患者的临床信息。在正常和肿瘤样本之间鉴定了差异表达的 miRNA。通过生存分析，构建了用于预测 PAAD 患者总生存期 (OS) 的 4 个 miRNA 特征。应用接收者操作特征 (ROC) 分析来确定生存预测的效率。此外，通过生物信息学方法评估了预测的 miRNA 的生物学功能。在 17 个差异表达的 miRNA 中，有 4 个（hsa-mir-126、hsa-mir-3613、hsa-mir-424 和 hsa-mir-4772）与 PAAD 患者的 OS 相关。此外，与 PAAD 患者 2 年生存率相关的构建的 4 个 miRNA 特征的曲线下面积 (AUC) 为 0.789。多变量 Cox 比例风险回归模型表明，该 4 个 miRNA 特征是 PAAD 患者其他临床参数的独立预后因素。进一步的通路富集分析表明，4 个 miRNA 特征中的 miRNA 可能调节影响焦点黏附、Wnt 信号通路和 PI3K-Akt 信号通路的基因。因此，这些发现表明，该 4 个 miRNA 特征可能是预测 PAAD 患者生存的有效独立预后生物标志物。
