Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels ofNPTX2were examined. The DNA methylation rate of theNPTX2gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level ofNPTX2was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with highNPTX2DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.
胸腺上皮性肿瘤（TET）包括胸腺瘤、胸腺癌（TC）和胸腺神经内分泌肿瘤（NECTT）。TET的遗传和表观遗传改变已成为近期研究的热点。本研究对TET中异常甲基化的CpG岛进行了全基因组筛查，发现与胸腺瘤相比，神经元五聚蛋白2（NPTX2）在TC中呈现显著高甲基化状态。NPTX2由突触前细胞响应神经元活动/癫痫发作而释放，在宿主免疫和急性炎症中发挥作用。研究收集了38例胸腺瘤、25例TC和6例NECTT样本，检测了NPTX2的DNA甲基化水平、mRNA及蛋白表达水平。结果显示，除B3型胸腺瘤外，TC中NPTX2基因的DNA甲基化率显著高于正常胸腺组织和胸腺瘤；TC中NPTX2的mRNA表达水平低于正常胸腺组织；mRNA表达水平与甲基化水平呈负相关关系。高NPTX2 DNA甲基化水平患者的无复发生存期较低甲基化水平者更短。NECTT则表现出极高的NPTX2 mRNA和蛋白表达水平及较低的DNA甲基化水平。研究表明，NPTX2可能在TC中发挥抑癌作用，而在NECTT中具有促癌功能。
Aberrant DNA Methylation of NPTX2 as an Indicator of Malignant Behavior in Thymic Epithelial Tumors
肿瘤(癌症)患者之家