Fusobacterium nucleatum Load Correlates with KRAS Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma.

Autor:	Takeda K; Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan., Koi M; Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.; Divsion of Gastroenterology and Hepatology, Department of Medicine and Moores Cancer Center, University of California San Diego, San Diego, California., Okita Y; Department of Gastrointestinal and Pediatric Surgery, Graduate School of Medicine, Mie University, Mie, Japan., Sajibu S; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland., Keku TO; Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Carethers JM; Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.; Divsion of Gastroenterology and Hepatology, Department of Medicine and Moores Cancer Center, University of California San Diego, San Diego, California.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2023 Sep 26; Vol. 3 (9), pp. 1940-1951.
DOI:	10.1158/2767-9764.CRC-23-0179
Abstrakt:	Fusobacterium nucleatum (Fn) has been frequently detected in colorectal cancer. A high load of Fn has been associated with subtypes of colorectal cancers, located in the proximal colon, exhibiting microsatellite instability-high (MSI-H), MLH1 promoter hypermethylation, the CpG island hypermethylation phenotype-high, or BRAF mutation in some studies. Although these features characterize the sessile serrated pathway (SSP) of colon cancers, other studies have shown that Fn infection is associated with KRAS mutations mainly characteristic of non-serrated neoplasia. It is also not clear at what point the association of Fn infection with these genomic alterations is established during colorectal carcinogenesis. Here we show that MSI-H, MLH1 hypermethylation, BRAF mutation or KRAS mutations were independently associated with Fn infection in colorectal cancer. On the other hand, increasing Fn copy number in tissues was associated with increased probability to exhibit MSI-H, MLH1 hypermethylation or BRAF mutations but not KRAS mutations in colorectal cancer. We also show that Fn load was significantly less than that of colorectal cancer and no association was detected between BRAF/KRAS mutations or MLH1 hypermethylation and Fn infection in adenomas. Our combined data suggest that increasing loads of Fn during and/or after adenomacarcinoma transition might promote SSP but not KRAS-driven colorectal carcinogenesis. Alternatively, Fn preferentially colonizes colorectal cancers with SSP and KRAS mutations but can expand more in colorectal cancers with SSP. Significance: The authors demonstrated that Fn is enriched in colorectal cancers exhibiting the SSP phenotype, and in colorectal cancers carrying KRAS mutations. Fn infection should be considered as a candidate risk factor specific to colorectal cancers with the SSP phenotype and with KRAS mutations. (© 2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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