Development of Personalized Therapy for Pancreatic Cancer Based on the Exploration of Composite Biomarkers from Both Tumor and Host Perspectives

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16475
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Nakajima Masao 山口大学, 医学部附属病院, 診療助教(4日/週) (00875487)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: PDAC / PBMC / tumor marker / gene expression

Outline of Final Research Achievements

This study has elucidated the following two key findings in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC): 1) Different types of NAC lead to variations in PBMC changes. 2) By analyzing changes in tumor markers and PBMC gene expression before and after NAC, it is possible to predict early postoperative distant metastasis recurrence. Specifically, it was found that patients whose CA19-9 levels do not decrease to normal and those with significant changes in the expression of gene X in PBMC before and after NAC are more likely to experience distant metastasis recurrence postoperatively. Furthermore, integrating the analysis results of CA19-9 and PBMC suggests a higher probability of predicting postoperative distant metastasis recurrence more accurately.

Free Research Field

Hepato-Biliary-Pancreatic Surgery

Academic Significance and Societal Importance of the Research Achievements

本研究により、術前化学療法後に腫瘍マーカーであるCA19-9が正常値まで下がらない膵癌症例は、術後に遠隔転移再発の可能性が高いことが示唆された。これにより、原発巣の切除を行わないという新たな治療方針の策定の可能性が示された。さらに、この基準に加えて、術前後の末梢血単核細胞（PBMC）の変化を解析することにより、術後早期再発を高確率で予測し、不要な手術を回避する可能性が示唆された。このアプローチは、個別化した集学的治療提供のコンセプト確立に寄与するものであり、学術的・社会的に意義ある成果を得た。また、これら高リスク症例に対して化学療法を継続することで、膵癌治療全体の成績向上が期待される。