TRIM38非CpG岛DNA甲基化与胶质瘤异柠檬酸脱氢酶突变的关系研究
作者:
作者单位:

1.延安大学医学院,陕西 延安 716000;2.空军军医大学 生物化学与分子生物学实验室,陕西 西安 710032;3.空军军医大学西京医院 神经外科,陕西 西安 710032

作者简介:

胡维红(1995—),女,硕士在读,主要从事胶质瘤表观遗传机制基础研究。

通信作者:

张静(1982—),男,教授,博士,主要从事肿瘤的表观遗传学研究,电话:0911-2331261 邮箱:yadxzj@163.com。

基金项目:

中国博士后科学基金(2019M653971);山东省自然科学基金青年项目(ZR2020QH233)


Association between non-CpG island DNA methylation of TRIM38 and isocitrate dehydrogenase gene mutations in glioma
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Affiliation:

1.Medical College of Yanan University, Yan’an, Shaanxi 716000, China;2.Department of Biochemistry and Molecular Biology, Air Force Military Medical University, Xi’an, Shaanxi 710032, China;3.Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi 710032, China

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    摘要:

    目的 探讨TRIM38基因非CpG岛DNA甲基化与胶质瘤异柠檬酸脱氢酶(IDH)基因突变之间的关系。方法 利用中国胶质瘤基因组图谱计划(CGGA)数据库的多组学数据和临床资料,比较在IDH野生型或突变型的胶质瘤中,TRIM38非CpG岛DNA甲基化的改变模式以及与基因表达和临床预后的关系。结果 共纳入CGGA胶质瘤325例及非肿瘤对照脑组织(NTB组)11例,分析发现IDH野生型胶质瘤TRIM38非CpG岛DNA甲基化和基因表达,相对NTB组分别发生低甲基化(P =0.000)和高表达(P=0.007),且两者之间呈负相关(P=0.017)。生存分析显示,TRIM38非CpG岛DNA甲基化水平与IDH野生型肿瘤的预后有关(P=0.061)。结论 IDH突变可能通过限制TRIM38基因非CpG岛DNA低甲基化介导的肿瘤促癌基因表达上调,为IDH突变相关的胶质瘤提供“保护作用”。

    Abstract:

    Objective To investigate the association between non-CpG island DNA methylation of TRIM38 and isocitrate dehydrogenase (IDH) gene mutations in glioma.Methods The multi-omics and clinical data from Chinese Glioma Genome Atlas (CGGA) were used to compare the differences in the non-CpG island DNA methylation pattern of TRIM38 and its association with gene expression and clinical prognosis between glioma with wild-type or mutant-type IDH.Results A total of 325 patients with glioma and 11 non-tumor brain (NTB) tissue samples from CGGA were included for analysis. It was found that compared with the NTB tissue samples, the glioma with wild-type IDH had a significant reduction in the non-CpG island DNA methylation of TRIM38P =0.000) and a significant increase in the gene expression of TRIM38P =0.007), with a significant negative correlation between them (P =0.017). The survival analysis showed that the non-CpG island DNA methylation level of TRIM38 was associated with the prognosis of glioma with wild-type IDHP = 0.061).Conclusions IDH mutations might exert a “protective effect” on gliomas associated with IDH mutation by inhibiting the upregulated expression of pro-oncogenic genes mediated by the non-CpG island DNA hypomethylation of TRIM38.

    图1 TRIM38基因非CpG岛DNA甲基化和基因表达在IDH突变型或野生型胶质瘤中的改变模式和相互关系Fig.1
    图2 TRIM38基因非CpG岛DNA甲基化与不同胶质瘤患者总体生存时间的关系Fig.2
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胡维红,吴元明,殷安安,张静456.TRIM38非CpG岛DNA甲基化与胶质瘤异柠檬酸脱氢酶突变的关系研究[J].国际神经病学神经外科学杂志,2021,48(5):415-418111HU Wei-Hong, WU Yuan-Ming, YIN An-An, ZHANG Jing222. Association between non-CpG island DNA methylation of TRIM38 and isocitrate dehydrogenase gene mutations in glioma[J]. Journal of International Neurology and Neurosurgery,2021,48(5):415-418

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  • 收稿日期:2021-04-19
  • 最后修改日期:2021-09-28
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  • 在线发布日期: 2021-11-15
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