Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes involved in the regrowth of clinically non-functioning pituitary adenoma
Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes involved in the regrowth of clinically non-functioning pituitary adenoma
复制标题
DNA 甲基化和 mRNA 表达谱的综合分析，以确定参与临床无功能垂体腺瘤再生的关键基因
DOI：
10.18632/aging.102751
复制
发表时间：
2020-02-15
期刊：
影响因子：
5.2
通讯作者：
Zhang, Yazhuo
中科院分区：
文献类型：
--
作者：
Cheng, Sen;Li, Chuzhong;Zhang, Yazhuo
肿瘤再生长是临床无功能垂体腺瘤（NFPA）的一个关键特征。对于术后患者，尚无适用的预后评估方法。我们的目的是确定DNA甲基化生物标志物，可以促进预后评估。对71例NFPA患者的肿瘤样本进行全基因组DNA甲基化和mRNA微阵列分析。基于再生长与非再生长分组，鉴定差异表达基因和甲基化基因。有139个基因的甲基化状态和表达水平发生了变化，只有13个基因的甲基化状态和表达水平呈负相关。无进展分析发现FAM 90 A1、ETS 2、STAT 6、MYT 1 L、ING 2和KCNK 1与肿瘤再生长有关。基于来自综合分析的所有13个基因建立了一个预测模型，6个基因模型的最佳受试者工作特征曲线下面积（AUC）为0.820，而13个基因和7个基因模型的AUC分别为0.785和0.568。我们的预后生物标志物通过焦磷酸测序和RT-PCR进行验证。单因素考克斯回归分析发现FAM 90 A1和ING 2是肿瘤再生长的独立预后因素。FAM 90 A1和ING 2基因的甲基化和表达水平与肿瘤的再生长有关，可作为预测NFPA患者预后的生物标志物。
Tumour regrowth is a key characteristic of clinically non-functioning pituitary adenoma (NFPA). No applicable prognosis evaluation method is available for post-operative patients. We aimed to identify DNA methylation biomarkers that can facilitate prognosis evaluation. Genome-wide DNA methylation and mRNA microarray analyses were performed for tumour samples from 71 NFPA patients. Differentially expressed genes and methylated genes were identified based on the regrowth vs non-regrowth grouping. There were 139 genes that showed alterations in methylation status and expression level, and only 13 genes showed a negative correlation. The progression-free analysis found that FAM90A1, ETS2, STAT6, MYT1L, ING2 and KCNK1 are related to tumour regrowth. A prognosis-prediction model was built based on all 13 genes from integrated analysis, and the 6-gene model achieved the best area under the receiver operating characteristic curves (AUC) of 0.820, compared with 0.785 and 0.568 for the 13-gene and 7-gene models, respectively. Our prognostic biomarkers were validated by pyrosequencing and RT-PCR. FAM90A1 and ING2 was found to be independent prognostic factors of tumour regrowth with univariate Cox regression. The DNA methylation and expression levels of FAM90A1 and ING2 are associated with tumour regrowth, and may serve as biomarkers for predicting the prognosis of patients with NFPA.