Subclassification of dMMR/MSI-H colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08802
• 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: Fukushima Medical University
• Principal Investigator: Sakamoto Wataru 福島県立医科大学, 医学部, 講師 (40622337)
• Co-Investigator(Kenkyū-buntansha): 岡山 洋和 福島県立医科大学, 医学部, 講師 (20583397)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸癌 / MSI / dMMR

Outline of Final Research Achievements

Colorectal cancer (CRC) exhibiting mismatch repair deficiency and/or microsatellite instability-High (dMMR/MSI-H) accounts for 15% of all CRCs and 4% of metastatic and recurrent cases. However, dMMR/MSI-H encompasses a broad spectrum with partially overlapping and contradictory characteristics, and this heterogeneity cannot be fully explained by known genomic, epigenomic, transcriptomic, or immunological factors, such as BRAF, CIMP, RAS, CMS, TMB, PDL1, CD8+TIL. The aim of this study was to identify distinct subgroups of dMMR/MSI-H CRC that enable individualized treatment. We have attempted to elucidate this issue using multiple RNA-seq, microarray and immunohistochemistry datasets with in vitro assays. Although we have obtained some intriguing findings, we are continuing our investigation.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤を中心とした免疫療法の登場から、dMMR/MSI-Hは臨床医に広く認知されるようになり、国内外で基礎研究・臨床研究が盛んに行われている。本研究の知見を今後さらに深め、発展させることで、dMMR/MSI-Hにおける新規のサブタイプを同定することができれば、大腸癌治療の個別化のための礎として寄与し得る可能性がある。