Comprehensive Gene Expression Analysis of Submucosal Invasion in Early Gastric Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15959
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: NAGAO Sayaka 東京大学, 医学部附属病院, 届出研究員 (30908299)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 胃癌 / 粘膜下層浸潤 / DEFA5 / STAT3

Outline of Final Research Achievements

To elucidate the mechanism of submucosal invasion in early gastric cancer, we performed microarray analysis and immunohistochemical staining. As a result, the expression of the antimicrobial peptide DEFA5 was significantly decreased in gastric cancers with submucosal invasion. On the other hand, pSTAT3, a downstream component of the JAK-STAT pathway, was upregulated in gastric cancers with submucosal invasion, and pSTAT3 was highly expressed in the areas where DEFA5 was downregulated. DEFA5 is important for maintaining intestinal microbiota homeostasis, and its downregulation could alter the intestinal environment, activating STAT3 and promoting cancer invasion.

Free Research Field

早期胃癌

Academic Significance and Societal Importance of the Research Achievements

本研究では、網羅的遺伝子発現解析により、早期胃癌の粘膜下層浸潤に関与する分子機構として、DEFA5発現低下とSTAT3活性化が関与している可能性が示唆された。DEFA5は腸内細菌叢制御に重要だが、癌浸潤への関与を示唆する知見が得られた点は学術的に意義深い。
本研究結果は、早期胃癌の進行機構解明に寄与する可能性を秘めており、早期胃癌の治療方針決定の精度向上とさらなる治療成績の改善につながることが期待される。