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ID 116971
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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
著者
テグシー, ビルグーン 徳島大学大学院保健科学教育部(保健学専攻)
Soejima, Shiho Tokushima University
Muguruma, Kyoka Tokushima University
キーワード
ghrelin
GHSR
In‑1 ghrelin
thymoma
thymic carcinoma
thymic epithelial tumors
資料タイプ
学位論文
抄録
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.
掲載誌名
Oncology Letters
ISSN
17921074
17921082
出版者
Spandidos Publications
22
5
開始ページ
793
発行日
2021-09-17
備考
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。
権利情報
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
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3608号
学位記番号
甲保第56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