Li Shengyue, Wang Lei, Zhao Qiang, Wang Zhihao, Lu Shuxian, Kang Yani, Jin Gang, Tian Jing
Key laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, China.
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Front Genet. 2020 Dec 2;11:596078. doi: 10.3389/fgene.2020.596078. eCollection 2020.
As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (-value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including , , , , , , , and . In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer.
作为最具侵袭性的癌症之一，胰腺癌由于缺乏有效的早期诊断方法而难以治疗。因此，迫切需要找到可靠的诊断和预测标志物用于胰腺癌的早期检测。近年来，血浆中循环游离DNA（cfDNA）甲基化的检测因其在癌症无创和早期诊断方面的潜力而受到全球关注。在此，我们通过甲基化DNA免疫沉淀结合高通量测序（MeDIP-seq）对胰腺导管腺癌（PDAC）患者进行了全基因组cfDNA甲基化谱研究。与健康个体相比，在PDAC患者中鉴定出775个位于启动子区域的差异甲基化区域（DMR），其中761个区域甲基化程度升高，14个区域甲基化程度降低；同时，在PDAC患者中鉴定出761个位于CpG岛（CGI）的DMR，其中734个区域甲基化程度升高，27个区域甲基化程度降低（P值<0.0001）。然后，进一步选择了143个位于启动子区域且与CGI完全重叠的高甲基化DMR。在应用最小绝对收缩和选择算子（LASSO）方法后，共发现8个标志物能够较好地区分PDAC患者和健康个体，包括……（此处原文未完整列出标志物名称）。总之，这项工作鉴定出一组8个差异甲基化标志物，可能潜在地应用于胰腺癌的无创诊断。
