| Project/Area Number |
17K15640
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
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| Research Institution | Shinshu University |
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Principal Investigator |
Yamanoi Kazuhiro 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教(特定雇用) (80464965)
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| Research Collaborator |
Nakayama Jun
Fujii Chifumi
Ohya Ayumu
Ida Koichi
Ishii Keiko
Asaka Shiho
Shimojo Hisashi
Miyamoto Tsutomu
Shiozawa Tanri
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 幽門腺 / 粘液 / 糖鎖 / がん / 病理診断 / αGlcNAc / MUC6 / HIK1083 / 幽門腺型粘液 / LEGH / 胃型腺癌 / MDA / 診断病理学 |
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| Outline of Final Research Achievements |
Gastric pyloric glands characteristically contain O-glycans having α1,4-linked N-acetylglucosamine residue (αGlcNAc) largely attached to MUC6 scaffold. In normal human gastric mucosa, αGlcNAc and MUC6 are co-expressed in pyloric gland cells. We examined αGlcNAc and MUC6 expression in human gastric, pancreas and uterine cervical tumors. We showed that reduced αGlcNAc expression relative to MUC6 was observed not only in invasive carcinoma lesions but also in their pre-malignant lesions, such as high-grade pyloric gland adenoma, high-grade intraepithelial neoplasia, high-grade intraductal papillary-mucinous neoplasm and atypical lobular endocervical gland hyperplasia. These results indicate that reduced αGlcNAc expression has already started in pre-malignant status in these organs. Thus, αGlcNAc could serve as a critical biomarker for malignant potential in early stage of gastric, pancreas and uterine cervical neoplasms.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、幽門腺型粘液に特異的な糖鎖修飾であるα1,4-linked N-acetylglucosamine(αGlcNAc)の消失が、胃や膵臓、子宮頸部の腫瘍において、浸潤がんだけでなく、その前がん状態から起きていることが明らかになった。
近年のがん診断、治療デバイスの進歩によって、腫瘍の早期病変の病理診断が非常に重要になっている。本研究成果にて、胃、膵臓、子宮頸部の病理標本でαGlcNAcの発現を確認すれば、腫瘍の早期診断に役立つことが示された。また、糖鎖修飾の変化と腫瘍の悪性度の関連を示した本成果により、糖鎖の変化を基盤とした、新たながん悪性化の機序が明らかにされる可能性が考えられる。
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