The possibility of urinary circulating tumor DNA predicting the effect of chemotherapy and recurrence risk after curative resection in colorectal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nippon Medical School
• Principal Investigator: Ohta Ryo 日本医科大学, 医学部, 講師 (30839824)
• Co-Investigator(Kenkyū-buntansha): 山田 岳史 日本医科大学, 医学部, 准教授 (50307948)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 尿循環腫瘍DNA / 大腸癌

Outline of Final Research Achievements

Plasma and urinary ctDNA concentrations were verified by stage in colorectal cancer cases. Furthermore, KRAS mutations were analyzed by digital PCR, and the sensitivity of plasma and urinary ctDNA, and differences by stage were examined. The results showed significantly lower concentrations of ctDNA in urine. Plasma ctDNA concentrations increased in a stage-dependent manner, however, urine ctDNA concentrations did not show a consistent trend. Digital PCR had similar sensitivities to identify KRAS mutations in plasma and urine. Urinary ctDNA sensitivity was significantly better in Stage I-III. Integrated analysis of plasma and urine ctDNA significantly increased identification sensitivity. KRAS mutations were also identified in plasma or urine ctDNA in 10.3% of cases in which KRAS mutations were not identified.

Free Research Field

大腸癌遺伝子変異解析

Academic Significance and Societal Importance of the Research Achievements

本研究は、尿ctDNAは非侵襲的に血漿ctDNAと同等の解析が可能であり、血漿ctDNAとの統合解析にてより感度が上昇し、腫瘍組織では同定不能なheterogeneityを検出することが可能であることを証明した重要な研究であることが確認された。腫瘍組織の一部から検出した遺伝子変異の有無により分子標的治療薬導入の可否を決定する場合には正確な解析が行われていない可能性があるため、尿ctDNAを用いることにより効果が見込めない化学療法を回避することが可能となるためその学術的・社会的意義は大きいと考えられた。