Kim Byoung-Chul, Jeong Hyoung Oh, Park Daeui, Kim Chul-Hong, Lee Eun Kyeong, Kim Dae Hyun, Im Eunok, Kim Nam Deuk, Lee Sunghoon, Yu Byung Pal, Bhak Jong, Chung Hae Young
Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea. ; Interdisciplinary Research Program of Bioinformatics and Longevity Science, Pusan National University, Busan, Republic of Korea.
Genomictree Inc., Yuseong-gu, Daejeon, Republic of Korea.
Cancer Inform. 2015 Apr 20;14:47-54. doi: 10.4137/CIN.S16912. eCollection 2015.
The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1β, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression.
我们研究的目的是识别在胃腺癌（STAD）状态下差异表达的表观遗传标记。基于来自癌症基因组图谱（TCGA）的数据，我们能够检测出年轻（n = 14）和老年（n = 70）STAD患者甲基化模式的年龄相关差异以及基因和miRNA表达水平的变化。我们的分析确定了老年STAD患者中有323个基因上调和653个基因下调。我们还分别发现了76个具有年龄相关表达模式的miRNA和113个差异甲基化基因（DMG）。我们的进一步分析表明，显著上调的基因（n = 35）与细胞周期相关，而肌肉系统过程相关基因（n = 27）和细胞黏附相关基因（n = 57）下调。此外，通过比较基因和miRNA表达与甲基化变化，我们确定已知参与炎症反应和细胞生长的三个上调基因（ELF3、IL1β和MMP13）在启动子区域显著低甲基化。我们还在老年STAD患者中检测了与年龄相关的下调miRNA（hsa-mir-124-3、hsa-mir-204和hsa-mir-125b-2）的靶标候选物。这是首次使用高通量数据探索STAD年龄相关表观遗传生物标志物的研究结果报告，并为年龄相关的STAD进展所表现出的复杂临床病理状况提供了证据。
