Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway.

Abstract

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the "colorectal continuum" concept.

• Authors: Miki Ito, Shinichi Kanno, Katsuhiko Nosho, Yasutaka Sukawa, Kei Mitsuhashi, Hiroyoshi Kurihara, Hisayoshi Igarashi, Taiga Takahashi, Mami Tachibana, Hiroaki Takahashi, Shinji Yoshii, Toshinao Takenouchi, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shinomura
• Journal: International journal of cancer (Int J Cancer) Vol. 137 Issue 6 Pg. 1258-68 (Sep 15 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25703934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 UICC.

Chemical References

• MIRN31 microRNA, human
• MicroRNAs

Topics

• Aged
• Carcinogenesis (genetics)
• Cecum (microbiology, pathology)
• Colon (microbiology, pathology)
• Colorectal Neoplasms (genetics, microbiology, pathology)
• CpG Islands (genetics)
• DNA Methylation (genetics)
• Female
• Fusobacterium Infections (genetics, microbiology, pathology)
• Fusobacterium nucleatum (isolation & purification)
• Humans
• Male
• MicroRNAs (genetics)
• Microsatellite Instability