Zhang Wei, Shang Shuai, Yang Yingying, Lu Peiyao, Wang Teng, Cui Xinyi, Tang Xuexi
Department of Marine Ecology, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266003, P.R. China.
Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory of Oceanology for Marine Science and Technology, Qingdao, Shandong 266071, P.R. China.
Exp Ther Med. 2020 Apr;19(4):2963-2972. doi: 10.3892/etm.2020.8554. Epub 2020 Feb 26.
Pancreatic adenocarcinoma (PAAD) is a painful and fatal disease that undoubtedly remains a health care priority and offers significant therapeutic challenges. The significance of epigenetic modifications, including DNA methylation in tumor development, has gained the attention of researchers. Identifying DNA methylation-driven genes and investigating the mechanisms underlying the tumorigenesis of PAAD are of substantial importance for developing methods of physiological evaluation, treatment planning and prognostic prediction for PAAD. In the present study, a comprehensive analysis of DNA methylation and gene expression data from 188 clinical samples was performed to identify DNA methylation-driven genes in PAAD. In addition, the diagnostic and prognostic value of DNA methylation-driven genes was evaluated using receiver operating characteristic curve, survival and recurrence analyses. A total of 7 DNA methylation-driven genes, namely zinc finger protein 208 (ZNF208), eomesodermin (EOMES), prostaglandin D2 receptor (PTGDR), chromosome 12 open reading frame 42 (C12orf42), integrin subunit α 4 (ITGA4), dedicator of cytokinesis 8 and protein phosphatase 1 regulatory inhibitor subunit 14D (PPP1R14D), were identified. All of them may be used to diagnose PAAD with excellent specificity and sensitivity (area under curve, >0.8). Of the 7 DNA methylation-driven genes, 6 were significantly associated with overall survival (OS) and recurrence-free survival (RFS) P<0.05). Among them, ZNF208, EOMES, PTGDR, C12orf42 and ITGA4 were significantly negatively associated with the OS rate and positively associated with the recurrence rate, while PPP1R14D was significantly positively associated with the OS rate and negatively associated with the recurrence rate. The present study provides novel insight into the epigenetic alterations associated with the occurrence and progression of PAAD, thereby increasing the mechanistic understanding of this disease, offering potential novel molecular biomarkers and contributing to the development of therapeutic targets for PAAD.
胰腺腺癌（PAAD）是一种痛苦且致命的疾病，无疑仍是医疗保健的重点，并且带来了重大的治疗挑战。表观遗传修饰的重要性，包括DNA甲基化在肿瘤发生中的作用，已引起研究人员的关注。识别DNA甲基化驱动的基因并研究PAAD肿瘤发生的潜在机制，对于开发PAAD的生理评估、治疗规划和预后预测方法至关重要。在本研究中，对188份临床样本的DNA甲基化和基因表达数据进行了全面分析，以识别PAAD中DNA甲基化驱动的基因。此外，使用受试者工作特征曲线、生存和复发分析评估了DNA甲基化驱动基因的诊断和预后价值。共鉴定出7个DNA甲基化驱动基因，即锌指蛋白208（ZNF208）、胚外中胚层决定因子（EOMES）、前列腺素D2受体（PTGDR）、12号染色体开放阅读框42（C12orf42）、整合素亚基α4（ITGA4）、胞质分裂8的专一性蛋白和蛋白磷酸酶1调节抑制剂亚基14D（PPP1R14D）。所有这些基因都可用于诊断PAAD，具有出色的特异性和敏感性（曲线下面积>0.8）。在这7个DNA甲基化驱动基因中，有6个与总生存期（OS）和无复发生存期（RFS）显著相关（P<0.05）。其中，ZNF208、EOMES、PTGDR、C12orf42和ITGA4与OS率显著负相关，与复发率正相关，而PPP1R14D与OS率显著正相关，与复发率负相关。本研究为与PAAD发生和进展相关的表观遗传改变提供了新的见解，从而加深了对该疾病机制的理解，提供了潜在的新型分子生物标志物，并有助于开发PAAD的治疗靶点。
