Soejima Shiho, Kondo Kazuya, Tsuboi Mitsuhiro, Muguruma Kyoka, Tegshee Bilguun, Kawakami Yukikiyo, Kajiura Koichiro, Kawakita Naoya, Toba Hiroaki, Yoshida Mitsuteru, Takizawa Hiromitsu, Tangoku Akira
Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8509, Japan.
Department of Thoracic, Endocrine Surgery and Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.
Oncol Lett. 2021 Jun;21(6):483. doi: 10.3892/ol.2021.12744. Epub 2021 Apr 21.
Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene () was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. catalyzes the production of γ-aminobutyric acid from L-glutamic acid. expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of were significantly higher in TC tissues than in thymomas. Patients with TET with high DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.
胸腺上皮肿瘤（TETs）包括胸腺瘤和胸腺癌（TC）。与胸腺瘤相比，胸腺癌具有更具侵袭性的特征和更差的预后。人们对胸腺瘤和胸腺癌中的基因和表观遗传改变进行了研究，试图确定胸腺癌的新靶点分子。在本研究中，对胸腺瘤和胸腺癌中异常甲基化的CpG岛进行了全基因组筛选，谷氨酸脱羧酶1基因（）被确定为与胸腺瘤相比在胸腺癌中第4个显著高甲基化的CpG岛。催化从L-谷氨酸产生γ-氨基丁酸。在大脑中表达丰富，但在包括胸腺在内的其他组织中很少见。1990年至2017年期间，从德岛大学医院接受手术或活检的90例患者中获取了73例胸腺瘤和17例胸腺癌组织。通过亚硫酸氢盐焦磷酸测序检测DNA甲基化，并分别使用逆转录定量PCR和免疫组织化学分析的mRNA和蛋白表达水平。胸腺癌组织中的DNA甲基化水平显著高于正常胸腺和胸腺瘤组织，甲基化对区分胸腺癌和胸腺瘤具有高敏感性和特异性。胸腺癌组织中的mRNA和蛋白表达水平显著高于胸腺瘤。DNA高甲基化以及mRNA和蛋白表达水平高的胸腺上皮肿瘤患者的无复发生存率显著低于水平低的患者。总之，与胸腺瘤相比，在胸腺癌组织中观察到明显更多的表观遗传改变，这可能有助于患者的临床特征和预后。
