Exploring molecular biological mechanisms involved in SATB2 expression in IBD-related neoplasms

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16170
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Shinshu University
• Principal Investigator: Iwaya Mai 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70850361)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 炎症性腸疾患 / 大腸癌 / SATB2 / 炎症性発癌 / Claudin 18.2

Outline of Final Research Achievements

To clarify the correlation between morphological and molecular biological findings in inflammatory bowel disease-associated carcinomas (CACs), immunohistochemical analysis, RNA sequencing, and DNA methylation analysis were performed. We found SATB2-negative CAC and SATB2-positive CAC have approximately 600 differentially expressed genes, and analyzed methylation patterns in the promoter region of the SATB2 gene. CAC tends to show gastric phenotype and we found that CAC significantly expresses Claudin 18.2. The findings suggest that CACs might be a candidate for zolbetuximab, an anti-Claudin 18.2 monoclonal antibody therapy

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

腸炎関連大腸癌（CAC）において、SATB2の陰転化が予後と相関する可能性が示されているが、SATB2陽性例と陰性例で、複数の遺伝子において有意に発現量が異なる事を明らかとし、CACにおいてSATB2が特異なバイオマーカーであることを検証した。今後、SATB2陰転化機序を明らかとすることで、CACの病態についてより迫れる可能性が高まった。また、CACでは散発性大腸癌と比して有意にClaudin18.2を発現している事を明らかとし、抗Claudin18.2抗体であるzolbetuximabがCACにおける治療選択肢となり得る可能性を示唆した。