TRIM38基因非CpG岛DNA甲基化与胶质母细胞瘤临床预后的关系

Impacts of TRIM38 non-CpG island DNA methylation alterations on clinical prognosis in patients with glioblastomas

目的探讨免疫基因TRIM38非CpG岛DNA甲基化在胶质母细胞瘤(GBM)中改变模式和临床意义。方法利用公共数据库,比较TRIM38甲基化在GBM与非肿瘤脑组织(NTB)中的差异程度,并通过统计分析探讨该基因甲基化水平与基因表达、病人预后、生物学背景的关系。结果纳入3组GBM(共509例)和3组NTB(共37例)样本。TRIM38基因非CpG岛DNA甲基化位点在GBM中呈低甲基化改变(P<0.05),而其基因表达呈现高表达改变(P<0.05),并且甲基化与基因表达呈显著负相关(P<0.05)。TRIM38低甲基化病人生存时间明显短于高甲基化组(P<0.05),甲基化水平是独立的预后影响因子(P<0.05)。TRIM38低甲基化GBM样本可能富集免疫调节及Toll样受体通路相关的基因簇。结论 TRIM38可能在GBM中通过非CpG岛低甲基化介导的基因异常表达上调,参与肿瘤发生、发展;TRIM38非CpG岛甲基化可能作为指导GBM预后评价的潜在生物标记物;TRIM38甲基化导致的预后差异很可能与Toll样受体通路及免疫调节的差异有关。

Objective To study the relationship of TRIM38 non-CpG island(CGI)DNA methylation with the prognosis in the patients with glioblastomas(GBMs).Methods By using experimental and clinical data acquired from the public databases,the degrees of DNA methylation of non-CGI open sea regions of TRIM38 in the GBMs tissues and non-tumor brains(NTB)tissues were analyzed and compared each other.The relationship of degrees of the methylation with the gene expression and prognosis in the patients with GBMs were analyzed.Results Three datasets of GBM(n=509)and NTB(n=37)were acquired respectively from the databases.The CpGs at non-CGI regions of TRIM38 was significantly hypomethylated in GBMs tissues compared that in NTB tissues(P<0.05).The DNA methylation of the CpGs was negatively related with TRIM38 expression(P<0.05).The included patients were divided into both the subgroups with TRIM38 hypermethylated and hypomethylated tumors.The overall survival time was significantly longer in the subgroup with hypermethylated tumors than that in the subgroup with hypomethylated tumors(P<0.05).The multivariate Cox models suggested that TRIM38 non-CGI DNA methylation was a independent factor related to the prognosis in the patients with GBMs(P<0.05).The bioinfomatic analysis showed that the subgroup with TRIM38 hypomethylated tumors was enriched with gene sets related to immune process regulation and toll-like receptors signaling.Conclusion Taking TRIM38 as an example,this study highlighted the potential significance of non-CGI DNA methylation alterations in gene expression and prognosis in the patients with GBMs.