Classification of BRAF V600E mutated colorectal cancer based on microsatellite stability

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16852
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Hospital Organization, Kyushu Cancer Center
• Principal Investigator: Nakano Michitaka 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 消化管・腫瘍内科医師 (30839478)
• Project Period (FY): 2020-03-01 – 2023-03-31
• Keywords: BRAF / MSI / colorectal cancer / immune checkpoint

Outline of Final Research Achievements

The study aims to stratify BRAF V600E mutated colorectal cancer which shows dismal prognosis by classifying them with immunogenicity. Particularly, discovering therapeutic targets in microsatellite stabie (MSS) tumor which is known to be less responsive to microsatellite instability high (MSI-H) is crucial for the personalized cancer therapy. We identified specific gene expression profiles on each of the subgroup by using 2 cohort build through TCGA and GEO database. Furthermore, nCounter gene expression panel analysis in our cohort with clinical data shows consistent data. These results will stratify the responder to checkpoint blockade in BRAF V600E mutated colorectal cancer, and discover the optimal therapeutic targets for low immunogenic BRAF V600E colorectal cancer.

Free Research Field

腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

本研究は予後不良であるBRAFV600E変異陽性(BRAF-mt)大腸がんを免疫プロファイリングに基づき分類し、新たな治療標的を探索することを目的としている。BRAF変異陽性大腸がんにおいて、免疫チェックポイント阻害薬に対する奏効群を抽出し、さらに非奏効群における最適な治療選択候補を探索することができるため、同患者群における個別化医療の推進が期待される。