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2022 Fiscal Year Final Research Report

Biological and clinical significance of transglutaminase 2 as a marker for early recurrence of hepatocellular carcinoma

Research Project

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Project/Area Number 18K15102
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionNihon University

Principal Investigator

YAMAGUCHI Hiromi  日本大学, 医学部, 客員研究員 (90547118)

Project Period (FY) 2018-04-01 – 2023-03-31
Keywordsトランスグルタミナーゼ2 / 肝細胞癌 / 早期再発 / Wnt/β-catenin signaling / TGF-β / がん微小環境
Outline of Final Research Achievements

To elucidate the TGM2 contribution to early hepatocellular carcinoma recurrence, We performed a comparative analysis between TGM2-high expression cell line (shCont) and TGM2-low expression cell line (shTGM2), derived from the liver cancer cell line JHH7. The shCont cells showed significantly higher cell proliferation ability and the lower mRNA levels of Wnt/β-catenin signal antagonists DKK family genes, compared to shTGM2. Recombinant hTGF-β1 stimulation resulted in an increase of TGM2 expression in both shControl and shTGM2 cells.
These results suggest that TGM2 may responds to signaling pathways changed under cancer-stromal interaction (such as Wnt/β-catenin pathway and TGF-β pathway) and indirectly contribute to tumor malignancy.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

TGM2が肝細胞癌早期再発群で高発現する意義と、再発に寄与するメカニズムは未知である。
今回、TGM2高発現の肝癌細胞は、Wnt/β-catenin pathwayやTGF-β pathwayに応答している可能性が示された。これらのsignaling pathwayはがん微小環境において重要な役割を果たしており、TGM2もこれらのpathwayの異常に連動して腫瘍の悪性化に間接的に寄与している可能性がある。今後は関連する分子の発現変化を観察することで肝細胞癌早期再発診断マーカーとしての有用性を確立し、また各シグナル伝達に関わる分子を標的とした肝細胞癌再発予防に繋がる可能性があるものと考える。

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Published: 2024-01-30  

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