A molecular analysis in colorectal poorly differentiated adenocarcinoma and its clinical application

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Aoki Hironori 札幌医科大学, 医学部, 訪問研究員 (40749496)
• Co-Investigator(Kenkyū-buntansha): 山本 英一郎 札幌医科大学, 医学部, 訪問研究員 (60567915)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 早期大腸がん / 低分化腺がん / 浸潤・転移 / トランスクリプトーム

Outline of Final Research Achievements

Submucosal invasion and lymph node metastasis are important issues affecting treatment options for early colorectal cancer (CRC). We performed RNA-sequencing (RNA-seq) with poorly differentiated components (PORs) and their normal counterparts isolated from T1 CRC tissues, and detected significant upregulation of SAA1 in PORs. Immunohistochemical analysis revealed that SAA1 was specifically expressed in PORs at the invasive front of T1b CRCs. Upregulation of SAA1 in CRC cells promoted cell migration and invasion. We also found that interleukin 1β (IL-1β) produced by macrophages induces SAA1 expression in CRC cells. Immunohistochemical analysis of primary T1 CRCs showed accumulation of macrophages at SAA1-positive invasive front regions. Our data suggest that macrophages at the invasive front of early CRCs promote cancer cell migration and invasion through induction of SAA1, and that SAA1 may be a predictive marker and a therapeutic target.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

我々は早期大腸低分化腺がんの解析から、SAA1が浸潤先進部の低分化成分に極めて特異的に発現することを見いだした。低分化腺がんは著しく進行が早いために早期で発見することは困難である。本研究は、最先端の消化管内視鏡診断技術をもつ専門施設と強力に連携することで初めて可能となった、独自性の高い研究である。本研究から、SAA1が早期大腸がんの予後予測マーカーや、治療標的となりうる可能性が示された。