Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran; Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.
Cancer Genet. 2021 Apr;252-253:64-72. doi: 10.1016/j.cancergen.2020.12.007. Epub 2020 Dec 30.
One of the most promising ways to diagnose cancer especially colorectal cancer (CRC) is to trace its epigenetic events. In this article, a discovery step for detection of methylated DNA markers (MDMs) was performed using SureSelectXT Methyl-Seq in CRC case and control groups in addition to several methylation profiling datasets (GSE48684, GSE53051, GSE77718, GSE101764, and GSE42752). In silico validation of MDMs in colorectal and other cancers was conducted by Lnc2met. MethyLight assay was run on 40 and 47 case and control formalin-fixed paraffin-embedded tissues, respectively and the performance of selected genes were classified by support vector machine (SVM). As a result, 180 regions were identified among all common genes. In addition to SEPT9 and SFRP2, the best three MDM regions were selected from SLC30A10, AKR1B1 and GALNT14. Based on all assays, the best performance was accomplished by SEPT9/AKR1B1 with 98% sensitivity, 99% specificity, 125 positive likelihood ratio, 0.02 negative likelihood ratio and 5074 diagnostic odds ratio. Our results indicate that the AKR1B1/SEPT9 methylation panel detects CRC with a higher performance than SEPT9 methylation, which is a commercial diagnostic test for CRC. However, the creation of a clinically valuable test derived from this study requires performance evaluation in liquid biopsies.
追踪癌症（尤其是结直肠癌，CRC）的表观遗传事件是诊断癌症的最有前途的方法之一。在本文中，我们在 CRC 病例组和对照组中使用 SureSelectXT Methyl-Seq 进行了检测甲基化 DNA 标志物（MDM）的发现步骤，此外还使用了多个甲基化分析数据集（GSE48684、GSE53051、GSE77718、GSE101764 和 GSE42752）。Lnc2met 对结直肠癌和其他癌症的 MDM 进行了计算机验证。MethyLight 检测在 40 个和 47 个病例和对照福尔马林固定石蜡包埋组织中分别进行，通过支持向量机（SVM）对选定基因的性能进行分类。结果，在所有常见基因中鉴定出 180 个区域。除 SEPT9 和 SFRP2 外，还从 SLC30A10、AKR1B1 和 GALNT14 中选择了最佳的三个 MDM 区域。基于所有检测，SEPT9/AKR1B1 的性能最佳，灵敏度为 98%，特异性为 99%，阳性似然比为 125，阴性似然比为 0.02，诊断比值比为 5074。我们的结果表明，AKR1B1/SEPT9 甲基化面板比 SEPT9 甲基化检测 CRC 的性能更高，SEPT9 甲基化是一种用于 CRC 的商业诊断测试。然而，从这项研究中创建一个具有临床价值的测试需要在液体活检中进行性能评估。
