Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul 08308, Korea.
Medical Science Research Center, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.
Curr Issues Mol Biol. 2021 Jun 28;43(2):501-512. doi: 10.3390/cimb43020038.
The incidence of nontuberculous (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis ( = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the "pathfinder" package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. was significantly less methylated, whereas 1 and were more methylated in patients with poor prognosis (compared to those with good prognosis). , , and were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1-cell differentiation, such as and , may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.
非结核分枝杆菌（NTM）肺病的发病率正在迅速上升；然而，在选择对适当治疗有反应的患者时，其诊断和预后仍不清楚。预后良好和预后不良的 NTM 患者之间 DNA 甲基化模式的差异可能为提供重要的治疗靶点。我们使用 Illumina MethylationEPIC（850k）DNA 甲基化微阵列来确定预后良好和预后不良的 NTM 患者（每组=4 人）之间差异甲基化区域（DMR）的模式。此外，我们合并并比较了之前 Illumina Methylation450k DNA 甲基化微阵列数据中的 20 个健康对照。我们以热图的形式选择和可视化 DMR，并通过使用“pathfinder”包进行功能注释来识别与这些 DMR 相关的富集术语。总共有 461 个和 293 个 DMR（|Log2 倍变化|>0.1 且 < 0.03）在四个预后不良和四个预后良好的患者中分别被更多地甲基化。此外，在 8 名 NTM 患者和 20 名健康对照中，分别有 337 个和 771 个 DMR（|Log2 倍变化|>0.08 且 < 0.001）被更多地甲基化。 显著较少甲基化，而 1 和 在预后不良的患者中被更多地甲基化（与预后良好的患者相比）。在 NTM 患者中， 、 和 是甲基化程度最低的前三个基因（与对照组相比）。mTOR 和 Wnt 信号通路相关基因在 NTM 患者中较少甲基化。总之，与 Th1 细胞分化相关的基因，如 和 ，可作为预测 NTM 肺病患者治疗反应的生物标志物。
