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ID 116971
Title Alternative
GHSR遺伝子のメチル化に関連するグレリン系バリアントリガンドと受容体の発現は胸腺腫の腫瘍形成を誘導する
EXPRESSION OF GHRELIN SYSTEM CONSTITUENTS IN THYMIC EPITHELIAL TUMORS
Author
Tegshee, Bilguun Tokushima University
Soejima, Shiho Tokushima University
Muguruma, Kyoka Tokushima University
Keywords
ghrelin
GHSR
In‑1 ghrelin
thymoma
thymic carcinoma
thymic epithelial tumors
Content Type
Thesis or Dissertation
Description
Our previous study reported that the DNA methylation of growth hormone secretagogue receptor (GHSR) was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin‑GHSR axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In‑1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O‑acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription‑quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In‑1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic‑adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In‑1 ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced‑stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In‑1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.
Journal Title
Oncology Letters
ISSN
17921074
17921082
Publisher
Spandidos Publications
Volume
22
Issue
5
Start Page
793
Published Date
2021-09-17
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Bilguun Tegshee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 4.0 International (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/)
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3608号
Diploma Number
甲保第56号
Granted Date
2022-03-23
Degree Name
Doctor of Health Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital