Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.
Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing Institute for Brain Disorders Brain Tumour Center, China National Clinical Research Center for Neurological Diseases, Key Laboratory of Central Nervous System Injury Research, Beijing 100070, China.
Aging (Albany NY). 2020 Feb 3;12(3):2408-2427. doi: 10.18632/aging.102751.
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 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. and was found to be independent prognostic factors of tumour regrowth with univariate Cox regression. The DNA methylation and expression levels of and are associated with tumour regrowth, and may serve as biomarkers for predicting the prognosis of patients with NFPA.
肿瘤复发是临床上无功能垂体腺瘤（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。我们旨在确定有助于预后评估的 DNA 甲基化生物标志物。对 71 例 NFPA 患者的肿瘤样本进行了全基因组 DNA 甲基化和 mRNA 微阵列分析。根据复发与非复发分组，鉴定差异表达的基因和甲基化基因。有 139 个基因显示甲基化状态和表达水平的改变，只有 13 个基因显示负相关。无进展分析发现与肿瘤复发相关的基因。基于综合分析的所有 13 个基因构建了预后预测模型，6 基因模型的受试者工作特征曲线（ROC）下面积（AUC）最佳，为 0.820，而 13 基因模型和 7 基因模型的 AUC 分别为 0.785 和 0.568。我们通过焦磷酸测序和 RT-PCR 验证了预后生物标志物。单因素 Cox 回归分析发现和是肿瘤复发的独立预后因素。和的 DNA 甲基化和表达水平与肿瘤复发相关，可能作为预测 NFPA 患者预后的生物标志物。
