GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

• 資料種別: 博士論文
• タイトル: GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors
• 著者・編者: Soejima, Shiho; Kondo, Kazuya; Tsuboi, Mitsuhiro; Muguruma, Kyoka; Tegshee, Bilguun; Kawakami, Yukikiyo; Kajiura, Koichiro; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Takizawa, Hiromitsu; Tangoku, Akira
• 著者標目: Soejima, Shiho; Kondo, Kazuya; Tsuboi, Mitsuhiro; Muguruma, Kyoka; Tegshee, Bilguun; Kawakami, Yukikiyo; Kajiura, Koichiro; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Takizawa, Hiromitsu; Tangoku, Akira
• 出版事項: Spandidos Publications
• 出版年月日等: 2021-04-21
• 出版年（W3CDTF）: 2021-04-21
• 並列タイトル等: 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
• タイトル（掲載誌）: Oncology Letters
• 巻号年月日等（掲載誌）: 21 6
• 掲載巻: 21
• 掲載号: 6
• 掲載ページ: 483-
• ISSN（掲載誌）: ISSN : 1792-1074; ISSN : 1792-1082
• 授与機関名: 徳島大学
• 授与年月日: 2022-03-23
• 報告番号: 甲第3607号
• 学位: 博士（保健学）
• 本文の言語コード: eng
• 件名標目: Thymic carcinoma (TC); thymoma; GAD1; DNA methylation; paradoxical expression; poor prognosis
• 対象利用者: 一般
• 一般注記: 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.
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: 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/).
• 関連情報（DOI）: 10.3892/ol.2021.12744
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/116970/20220511115405345638/k3607_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/116970/20220511115405433083/k3607_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/116970/20220511115405511670/k3607_fulltext.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/116970/20220511115405666178/k3607_supple.pdf fulltext