Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer.
Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer.
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DOI：
10.1016/j.csbj.2021.05.049
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发表时间：
2021
影响因子：
6
通讯作者：
Wakai T
中科院分区：
文献类型：
--
作者：
Okuda S;Shimada Y;Tajima Y;Yuza K;Hirose Y;Ichikawa H;Nagahashi M;Sakata J;Ling Y;Miura N;Sugai M;Watanabe Y;Takeuchi S;Wakai T
一些细菌在肿瘤组织中是共生的，已经发现几种细菌的代谢物会引起DNA损伤。然而，迄今为止，大肠直肠癌（CRC）中细菌和宿主遗传改变之间的关系尚未得到充分研究。我们评估了29名日本结直肠癌患者肿瘤内微生物组与宿主遗传改变之间的关系。提取患者的肿瘤组织和非肿瘤组织，对每个样本进行16S rRNA基因测序。我们在肿瘤和非肿瘤组织中发现了富集的细菌。一些细菌，如已知在结直肠癌中富集的梭杆菌，被发现在肿瘤组织中富集。有趣的是，已知在结直肠癌中也富集的拟杆菌在非肿瘤组织中也富集。此外，研究表明，肿瘤组织中经常共存的某些细菌在宿主细胞中存在突变基因或突变基因的信号通路时富集。梭杆菌与许多突变基因以及包括突变基因在内的细胞周期相关途径有关。此外，具有高丰度弯曲杆菌的患者被认为与突变标记3有关，这表明双链DNA断裂修复失败。这些结果表明，CRC的发展可能部分是由于细菌感染释放的物质引起的DNA损伤。综上所述，鉴定不同的肠道微生物组模式及其宿主特异性遗传改变可能有助于有针对性的干预，例如除了抗癌药物或免疫治疗外，还可以调节微生物组。
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.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
10.1
作者：
Hamada T;Zhang X;Mima K;Bullman S;Sukawa Y;Nowak JA;Kosumi K;Masugi Y;Twombly TS;Cao Y;Song M;Liu L;da Silva A;Shi Y;Gu M;Li W;Koh H;Nosho K;Inamura K;Keum N;Wu K;Meyerhardt JA;Kostic AD;Huttenhower C;Garrett WS;Meyerson M;Giovannucci EL;Chan AT;Fuchs CS;Nishihara R;Giannakis M;Ogino S
通讯作者：
Ogino S
影响因子：
3.9
作者：
Fukui, Hirokazu;Nishida, Akifumi;Miwa, Hiroto
通讯作者：
Miwa, Hiroto
影响因子：
2.3
作者：
Eifert, Cheryl;Pantazi, Angeliki;Protopopov, Alexei
通讯作者：
Protopopov, Alexei