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DNA methylome and transcriptome analysis established a model of four differentially methylated positions (DMPs) as a diagnostic marker in esophageal adenocarcinoma early detection
PeerJ ( IF 2.3 ) Pub Date : 2021-05-07 , DOI: 10.7717/peerj.11355
Weilin Peng 1, 2 , Guangxu Tu 1, 2 , Zhenyu Zhao 1, 2 , Boxue He 1, 2 , Qidong Cai 1, 2 , Pengfei Zhang 1, 2 , Xiong Peng 1, 2 , Shuai Shi 1, 2 , Xiang Wang 1, 2
Affiliation  

Background Esophageal carcinogenesis involves in alterations of DNA methylation and gene transcription. This study profiled genomic DNA methylome vs. gene expression using transcriptome data on esophageal adenocarcinoma (EAC) tissues from the online databases in order to identify methylation biomarkers in EAC early diagnosis. Materials and Methods The DNA methylome and transcriptome data were downloaded from the UCSC Xena, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases and then bioinformatically analyzed for the differentially methylated positions (DMPs) vs. gene expression between EAC and normal tissues. The highly methylated DMPs vs. reduced gene expression in EAC were selected and then stratified with those of the corresponding normal blood samples and other common human cancers to construct an EAC-specific diagnostic model. The usefulness of this model was further verified in other three GEO datasets of EAC tissues. Result A total of 841 DMPs were associated with expression of 320 genes, some of which were aberrantly methylated in EAC tissues. Further analysis showed that four (cg07589773, cg10474350, cg13011388 and cg15208375 mapped to gene IKZF1, HOXA7, EFS and TSHZ3, respectively) of these 841 DMPs could form and establish a diagnostic model after stratified them with the corresponding normal blood samples and other common human cancers. The data were further validated in other three GEO datasets on EAC tissues in early EAC diagnosis. Conclusion This study revealed a diagnostic model of four genes methylation to diagnose EAC early. Further study will confirm the usefulness of this model in a prospective EAC cases.

中文翻译:

DNA甲基化组和转录组分析建立了四个差异甲基化位置(DMP)模型作为食管腺癌早期检测的诊断标志物

背景 食管癌发生涉及 DNA 甲基化和基因转录的改变。本研究使用在线数据库中食管腺癌 (EAC) 组织的转录组数据对基因组 DNA 甲基化组与基因表达进行了分析,以识别 EAC 早期诊断中的甲基化生物标志物。材料和方法 从 UCSC Xena、基因表达综合 (GEO) 和癌症基因组图谱 (TCGA) 数据库下载 DNA 甲基化组和转录组数据,然后对 EAC 之间的差异甲基化位置 (DMP) 与基因表达进行生物信息分析。和正常组织。高度甲基化的 DMP 与 选择 EAC 中降低的基因表达,然后与相应的正常血液样本和其他常见人类癌症的基因进行分层,以构建 EAC 特异性诊断模型。该模型的实用性在其他三个 EAC 组织的 GEO 数据集中得到了进一步验证。结果共有841个DMPs与320个基因的表达相关,其中一些基因在EAC组织中异常甲基化。进一步分析表明,这841个DMP中的4个(cg07589773、cg10474350、cg13011388和cg15208375分别映射到基因IKZF1、HOXA7、EFS和TSHZ3)在与相应的正常血样和其他常见人类样本分层后可以形成并建立诊断模型癌症。这些数据在 EAC 早期诊断中 EAC 组织的其他三个 GEO 数据集中得到了进一步验证。结论 本研究揭示了一种早期诊断 EAC 的四种基因甲基化诊断模型。进一步的研究将证实该模型在前瞻性 EAC 病例中的有用性。
更新日期:2021-05-07
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