Saito Tatsushi, Karasawa Hideaki, Ouchi Kota, Ono Tomoyuki, Kajiwara Taiki, Kohyama Atsushi, Ikeda-Ohtsubo Wakako, Fukuda Shinji, Fujishima Fumiyoshi, Ozawa Yohei, Suzuki Hideyuki, Watanabe Kazuhiro, Ishioka Chikashi, Kamei Takashi, Ohnuma Shinobu, Abe Takaaki, Unno Michiaki
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-Ku, Sendai, 980-8574, Japan.
Department of Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-Ku, Sendai, 980-8574, Japan.
Int J Clin Oncol. 2025 Jun 16. doi: 10.1007/s10147-025-02812-3.
Epigenetic alterations, including DNA methylation, significantly contribute to colorectal cancer (CRC); the gut microbiota is also involved. However, studies on the possible role of microbiota in DNA methylation are limited. This study investigates the association between gut microbiota composition and high-methylated CRC (HMCC).
Fecal and tumor tissue samples were collected from 86 patients with sporadic CRC. HMCC was defined based on the methylation status of 16 CpG sites of tumor-derived genomic DNA. 16S rRNA gene sequencing was performed to reveal the composition of the gut microbiota. The load of Fusobacterium nucleatum (F. nucleatum) in tumor tissues was assessed using quantitative polymerase chain reaction (qPCR).
HMCC was identified in 21 patients, whereas 65 were classified as having low-methylated CRC (LMCC). HMCC was significantly associated with proximal location, large diameter, undifferentiated histology, and high frequency of BRAF mutation. In gut microbial analyses, the relative abundances of 84 bacteria, including F. nucleatum, were significantly different between HMCC and LMCC. The load of F. nucleatum in CRC specimens was significantly correlated with its relative abundance in fecal samples and tended to be enriched in HMCC tissues.
This study characterizes the gut microbiota profile in HMCC and suggests that bacteria, such as F. nucleatum, may contribute to HMCC pathogenesis through DNA methylation. Further studies are needed to determine whether the microbiome acts as a promoter or bystander in HMCC development.
包括DNA甲基化在内的表观遗传改变在结直肠癌（CRC）中起重要作用；肠道微生物群也参与其中。然而，关于微生物群在DNA甲基化中可能作用的研究有限。本研究调查肠道微生物群组成与高甲基化结直肠癌（HMCC）之间的关联。
收集86例散发性CRC患者的粪便和肿瘤组织样本。根据肿瘤来源基因组DNA的16个CpG位点的甲基化状态定义HMCC。进行16S rRNA基因测序以揭示肠道微生物群的组成。使用定量聚合酶链反应（qPCR）评估肿瘤组织中具核梭杆菌（F. nucleatum）的载量。
21例患者被鉴定为HMCC，而65例被归类为低甲基化结直肠癌（LMCC）。HMCC与肿瘤近端位置、大直径、未分化组织学和BRAF突变高频率显著相关。在肠道微生物分析中，包括具核梭杆菌在内的84种细菌的相对丰度在HMCC和LMCC之间存在显著差异。CRC标本中具核梭杆菌的载量与其在粪便样本中的相对丰度显著相关，并且在HMCC组织中倾向于富集。
本研究描绘了HMCC中的肠道微生物群特征，并表明诸如具核梭杆菌等细菌可能通过DNA甲基化促进HMCC发病机制。需要进一步研究以确定微生物群在HMCC发展中是起促进作用还是旁观者作用。
