TY - JOUR
T1 - Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer
AU - Okuda, Shujiro
AU - Shimada, Yoshifumi
AU - Tajima, Yosuke
AU - Yuza, Kizuki
AU - Hirose, Yuki
AU - Ichikawa, Hiroshi
AU - Nagahashi, Masayuki
AU - Sakata, Jun
AU - Ling, Yiwei
AU - Miura, Nobuaki
AU - Sugai, Mika
AU - Watanabe, Yu
AU - Takeuchi, Shiho
AU - Wakai, Toshifumi
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/1
Y1 - 2021/1
N2 - Some bacteria are symbiotic in tumor tissues, and metabolites of several bacterial species have been found to cause DNA damage. However, to date, the association between bacteria and host genetic alterations in colorectal cancer (CRC) has not been fully investigated. We evaluated the association between the intra-tumor microbiome and host genetic alterations in 29 Japanese CRC patients. The tumor and non-tumor tissues were extracted from the patients, and 16S rRNA genes were sequenced for each sample. We identified enriched bacteria in tumor and non-tumor tissues. Some bacteria, such as Fusobacterium, which is already known to be enriched in CRC, were found to be enriched in tumor tissues. Interestingly, Bacteroides, which is also known to be enriched in CRC, was enriched in non-tumor tissues. Furthermore, it was shown that certain bacteria that often coexist within tumor tissue were enriched in the presence of a mutated gene or signal pathway with mutated genes in the host cells. Fusobacterium was associated with many mutated genes, as well as cell cycle-related pathways including mutated genes. In addition, the patients with a high abundance of Campylobacter were suggested to be associated with mutational signature 3 indicating failure of double-strand DNA break repairs. These results suggest that CRC development may be partly caused by DNA damage caused by substances released by bacterial infection. Taken together, the identification of distinct gut microbiome patterns and their host specific genetic alterations might facilitate targeted interventions, such as modulation of the microbiome in addition to anticancer agents or immunotherapy.
AB - Some bacteria are symbiotic in tumor tissues, and metabolites of several bacterial species have been found to cause DNA damage. However, to date, the association between bacteria and host genetic alterations in colorectal cancer (CRC) has not been fully investigated. We evaluated the association between the intra-tumor microbiome and host genetic alterations in 29 Japanese CRC patients. The tumor and non-tumor tissues were extracted from the patients, and 16S rRNA genes were sequenced for each sample. We identified enriched bacteria in tumor and non-tumor tissues. Some bacteria, such as Fusobacterium, which is already known to be enriched in CRC, were found to be enriched in tumor tissues. Interestingly, Bacteroides, which is also known to be enriched in CRC, was enriched in non-tumor tissues. Furthermore, it was shown that certain bacteria that often coexist within tumor tissue were enriched in the presence of a mutated gene or signal pathway with mutated genes in the host cells. Fusobacterium was associated with many mutated genes, as well as cell cycle-related pathways including mutated genes. In addition, the patients with a high abundance of Campylobacter were suggested to be associated with mutational signature 3 indicating failure of double-strand DNA break repairs. These results suggest that CRC development may be partly caused by DNA damage caused by substances released by bacterial infection. Taken together, the identification of distinct gut microbiome patterns and their host specific genetic alterations might facilitate targeted interventions, such as modulation of the microbiome in addition to anticancer agents or immunotherapy.
KW - Campylobacter
KW - Colorectal cancer
KW - Fusobacterium
KW - Mutational signature
KW - Tumor microbiome
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U2 - 10.1016/j.csbj.2021.05.049
DO - 10.1016/j.csbj.2021.05.049
M3 - Article
AN - SCOPUS:85107849659
SN - 2001-0370
VL - 19
SP - 3330
EP - 3338
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -