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Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer 被引量:51
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作者 Katsuhiko Nosho Yasutaka Sukawa +11 位作者 Yasushi Adachi Miki Ito kei mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura 《World Journal of Gastroenterology》 SCIE CAS 2016年第2期557-566,共10页
The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alte... The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. 展开更多
关键词 BRAF CPG island methylator PHENOTYPE COLON NEOPLASIA FUSOBACTERIUM species miR-21
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MicroRNA-31 expression in colorectal serrated pathway progression 被引量:5
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作者 Hironori Aoki Katsuhiko Nosho +11 位作者 Hisayoshi Igarashi Miki Ito kei mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu Suzuki Hiroyuki Yamamoto Yasuhisa Shinomura 《World Journal of Gastroenterology》 SCIE CAS 2014年第34期12346-12349,共4页
MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in CRC.Moreover,... MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in CRC.Moreover,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated lesions.At a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated features.Tissue specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP component.Higher miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression. 展开更多
关键词 BRAF Colorectal carcinoma MicroRNA-31 MLH1 microsatellite instability Serrated pathway
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IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions
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作者 Takafumi Naito Katsuhiko Nosho +19 位作者 Miki Ito Hisayoshi Igarashi kei mitsuhashi Shinji Yoshii Hironori Aoki Masafumi Nomura Yasutaka Sukawa Eiichiro Yamamoto Yasushi Adachi Hiroaki Takahashi Masao Hosokawa Masahiro Fujita Toshinao Takenouchi Reo Maruyama Hiromu Suzuki Yoshifumi Baba Kohzoh Imai Hiroyuki Yamamoto Shuji Ogino Yasuhisa Shinomura 《World Journal of Gastroenterology》 SCIE CAS 2014年第29期10050-10061,共12页
AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.
关键词 BRAF Colon polyp Colorectal neoplasia COLORECTUM Genome Insulin-like growth factor Long interspersed nucleotide element-1 Microsatellite instability Serrated pathway
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