Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis

Tomomitsu Tahara, Ichiro Hirata, Naoko Nakano, Sayumi Tahara, Noriyuki Horiguchi, Tomohiko Kawamura, Masaaki Okubo, Takamitsu Ishizuka, Hyuga Yamada, Dai Yoshida, Takafumi Ohmori, Kohei Maeda, Naruomi Komura, Hirokazu Ikuno, Yasutaka Jodai, Toshiaki Kamano, Mitsuo Nagasaka, Yoshihito Nakagawa, Tetsuya Tuskamoto, Makoto Urano & 3 others Tomoyuki Shibata, Makoto Kuroda, Naoki Omiya

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of > 450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/ neg) samples (P < 0.01). Genes hypermethylated in FB-high samples included wellknown type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.

Original languageEnglish
Pages (from-to)61917-61926
Number of pages10
JournalOncotarget
Volume8
Issue number37
DOIs
Publication statusPublished - 01-09-2017

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Fusobacterium
DNA Methylation
Ulcerative Colitis
Methylation
Mucous Membrane
Genes
Colorectal Neoplasms
Genome
Neoplasms
Carcinogenesis
Multivariate Analysis
Odds Ratio
Confidence Intervals
Inflammation

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Tahara, Tomomitsu ; Hirata, Ichiro ; Nakano, Naoko ; Tahara, Sayumi ; Horiguchi, Noriyuki ; Kawamura, Tomohiko ; Okubo, Masaaki ; Ishizuka, Takamitsu ; Yamada, Hyuga ; Yoshida, Dai ; Ohmori, Takafumi ; Maeda, Kohei ; Komura, Naruomi ; Ikuno, Hirokazu ; Jodai, Yasutaka ; Kamano, Toshiaki ; Nagasaka, Mitsuo ; Nakagawa, Yoshihito ; Tuskamoto, Tetsuya ; Urano, Makoto ; Shibata, Tomoyuki ; Kuroda, Makoto ; Omiya, Naoki. / Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis. In: Oncotarget. 2017 ; Vol. 8, No. 37. pp. 61917-61926.
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abstract = "BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of > 450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/ neg) samples (P < 0.01). Genes hypermethylated in FB-high samples included wellknown type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95{\%} confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.",
author = "Tomomitsu Tahara and Ichiro Hirata and Naoko Nakano and Sayumi Tahara and Noriyuki Horiguchi and Tomohiko Kawamura and Masaaki Okubo and Takamitsu Ishizuka and Hyuga Yamada and Dai Yoshida and Takafumi Ohmori and Kohei Maeda and Naruomi Komura and Hirokazu Ikuno and Yasutaka Jodai and Toshiaki Kamano and Mitsuo Nagasaka and Yoshihito Nakagawa and Tetsuya Tuskamoto and Makoto Urano and Tomoyuki Shibata and Makoto Kuroda and Naoki Omiya",
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Tahara, T, Hirata, I, Nakano, N, Tahara, S, Horiguchi, N, Kawamura, T, Okubo, M, Ishizuka, T, Yamada, H, Yoshida, D, Ohmori, T, Maeda, K, Komura, N, Ikuno, H, Jodai, Y, Kamano, T, Nagasaka, M, Nakagawa, Y, Tuskamoto, T, Urano, M, Shibata, T, Kuroda, M & Omiya, N 2017, 'Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis', Oncotarget, vol. 8, no. 37, pp. 61917-61926. https://doi.org/10.18632/oncotarget.18716

Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis. / Tahara, Tomomitsu; Hirata, Ichiro; Nakano, Naoko; Tahara, Sayumi; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Yamada, Hyuga; Yoshida, Dai; Ohmori, Takafumi; Maeda, Kohei; Komura, Naruomi; Ikuno, Hirokazu; Jodai, Yasutaka; Kamano, Toshiaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Tuskamoto, Tetsuya; Urano, Makoto; Shibata, Tomoyuki; Kuroda, Makoto; Omiya, Naoki.

In: Oncotarget, Vol. 8, No. 37, 01.09.2017, p. 61917-61926.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis

AU - Tahara, Tomomitsu

AU - Hirata, Ichiro

AU - Nakano, Naoko

AU - Tahara, Sayumi

AU - Horiguchi, Noriyuki

AU - Kawamura, Tomohiko

AU - Okubo, Masaaki

AU - Ishizuka, Takamitsu

AU - Yamada, Hyuga

AU - Yoshida, Dai

AU - Ohmori, Takafumi

AU - Maeda, Kohei

AU - Komura, Naruomi

AU - Ikuno, Hirokazu

AU - Jodai, Yasutaka

AU - Kamano, Toshiaki

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Tuskamoto, Tetsuya

AU - Urano, Makoto

AU - Shibata, Tomoyuki

AU - Kuroda, Makoto

AU - Omiya, Naoki

PY - 2017/9/1

Y1 - 2017/9/1

N2 - BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of > 450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/ neg) samples (P < 0.01). Genes hypermethylated in FB-high samples included wellknown type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.

AB - BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of > 450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/ neg) samples (P < 0.01). Genes hypermethylated in FB-high samples included wellknown type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.

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U2 - 10.18632/oncotarget.18716

DO - 10.18632/oncotarget.18716

M3 - Article

VL - 8

SP - 61917

EP - 61926

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

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