Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2020 May 5;10(1):7559. doi: 10.1038/s41598-020-64569-1.
Pancreatic cancer (PC) is a malignancy with little/no warning signs before the disease reaches its ultimate stages. Currently early detection of PC is very difficult because most patients have non-specific symptoms leading to postponing the correct diagnosis. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant miRNA signatures helpful in diagnosis of PC and constructed novel miRNA diagnosis models for PC. Altogether, 27 differentially expressed miRNAs (DEMs) showed area under curve (AUC) score >80%. The most promising miRNAs, miR-1469 and miR-4530, were individually able to distinguish two groups with the highest specificity and sensitivity. By using multivariate cox regression analyses, 5 diagnostic models consisting of different combinations of miRNAs, based on their significant expression algorithms and functional properties were introduced. The correlation model consisting of miR-125a-3p, miR-5100 and miR-642b-3p was the most promising model in the diagnosis of PC patients from healthy controls with an AUC of 0.95, Sensitivity 0.98 and Specificity 0.97. Validation analysis was conducted for considered miRNAs on a final cohort consist of the microarray data from two other datasets (GSE112264 & GSE124158) . These results provide some potential biomarkers for PC diagnosis after testing in large case-control and cohort studies.
胰腺癌(PC)是一种恶性肿瘤,在疾病达到终末期之前几乎没有/没有警告信号。目前,PC 的早期检测非常困难,因为大多数患者的症状不具有特异性,导致正确诊断被推迟。在这项研究中,我们使用多种生物信息学工具,整合了各种 miRNA 的血清表达谱,以找到最有意义的 miRNA 特征,有助于 PC 的诊断,并构建了用于 PC 的新型 miRNA 诊断模型。总的来说,有 27 个差异表达的 miRNA(DEM)显示出 AUC 评分>80%。最有前途的 miRNA,miR-1469 和 miR-4530,能够单独区分两组,具有最高的特异性和敏感性。通过使用多元 Cox 回归分析,基于其显著表达算法和功能特性,提出了由不同 miRNA 组合组成的 5 个诊断模型。由 miR-125a-3p、miR-5100 和 miR-642b-3p 组成的相关模型是诊断 PC 患者与健康对照者的最有前途的模型,AUC 为 0.95,敏感性为 0.98,特异性为 0.97。在考虑 miRNA 的最终队列上进行了验证分析,该队列由来自两个其他数据集(GSE112264 和 GSE124158)的微阵列数据组成。这些结果为 PC 诊断提供了一些潜在的生物标志物,需要在大规模病例对照和队列研究中进行测试。