Total for the last 12 months
number of access : ?
number of downloads : ?
ID 116970
Title Alternative
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
Author
Soejima, Shiho Tokushima University
Muguruma, Kyoka Tokushima University
Tegshee, Bilguun Tokushima University
Keywords
Thymic carcinoma (TC)
thymoma
GAD1
DNA methylation
paradoxical expression
poor prognosis
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Oncology Letters
ISSN
17921074
17921082
Publisher
Spandidos Publications
Volume
21
Issue
6
Start Page
483
Published Date
2021-04-21
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3607号
Diploma Number
甲保第55号
Granted Date
2022-03-23
Degree Name
Doctor of Health Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital