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タイトル別表記
胸腺上皮性腫瘍における悪性度指標としてのGAD1の発現とメチル化の関係
GAD1 EXPRESSION AND DNA METHYLATION IN THYMIC EPITHELIAL TUMORS
著者
副島, 志帆 徳島大学大学院保健科学教育部(保健学専攻)
Muguruma, Kyoka Tokushima University
Tegshee, Bilguun Tokushima University
キーワード
Thymic carcinoma (TC)
thymoma
GAD1
DNA methylation
paradoxical expression
poor prognosis
資料タイプ
学位論文
抄録
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 (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ‑aminobutyric acid from L‑glutamic acid. GAD1 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 GAD1 were analyzed using reverse transcription‑quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 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.
掲載誌名
Oncology Letters
ISSN
17921074
17921082
出版者
Spandidos Publications
21
6
開始ページ
483
発行日
2021-04-21
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Shiho Soejimaの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3607号
学位記番号
甲保第55号
学位授与年月日
2022-03-23
学位名
博士(保健学)
学位授与機関
徳島大学
部局
医学系
病院