Li Gangping, Jin Yu, Chen Baolong, Lin Aiqiang, Wang Erchuan, Xu Fenghua, Hu Gengcheng, Xiao Chuanxing, Liu Hongli, Hou Xiaohua, Zhang Bangzhou, Song Jun
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiamen Treatgut Biotechnology Co., Ltd., Xiamen 361115, China.
Cancers (Basel). 2023 Jul 9;15(14):3555. doi: 10.3390/cancers15143555.
The fecal virome has been reported to be associated with CRC. However, little is known about the mucosal virome signature in CRC. This study aimed to determine the viral community within CRC tissues and their contributions to colorectal carcinogenesis. Colonic mucosal biopsies were harvested from patients with CRC (biopsies of both neoplasia and adjacent normal tissue (CRC-A)) and healthy controls (HC). The shot-gun metagenomic sequencing of virus-like particles (VLPs) was performed on the biopsies. Viral community, functional pathways, and their correlations to clinical data were analyzed. Fluorescence in situ hybridizations (FISH) for the localization of viruses in the intestine was performed, as well as quantitative PCR for the detection of Torque teno virus load in human mucosal VLP DNA. A greater number and proportion of core species were found in CRC tissues than in CRC-A and HC tissues. The diversity of the mucosal virome in CRC tissues was significantly increased compared to that in HC and CRC-A tissues. The mucosal virome signature of CRC tissues were significantly different from those of HC and CRC-A tissues at the species level. The abundances of eukaryotic viruses from the Anelloviridae family and its sub-species Torque teno virus (TTV) were significantly higher in CRC patients than in HC. Furthermore, increased levels of TTV in the intestinal lamina propria were found in the CRC group. Multiple viral functions of TTV associated with carcinogenesis were enriched in CRC tissues. We revealed for the first time that the mucosal virobiota signature of CRC is characterized by a higher diversity and more eukaryotic viruses. The enrichment of TTV species in CRC tissues suggests that they may play an oncogenic role in CRC. Targeting eukaryotic viruses in the gut may provide novel strategies for the prevention and treatment of CRC.
据报道，粪便病毒组与结直肠癌（CRC）有关。然而，关于CRC中的黏膜病毒组特征却知之甚少。本研究旨在确定CRC组织内的病毒群落及其对结直肠癌发生的作用。从CRC患者（肿瘤组织及相邻正常组织活检（CRC-A））和健康对照（HC）中采集结肠黏膜活检样本。对活检样本进行病毒样颗粒（VLP）的鸟枪法宏基因组测序。分析病毒群落、功能途径及其与临床数据的相关性。进行荧光原位杂交（FISH）以定位肠道中的病毒，并进行定量PCR以检测人黏膜VLP DNA中的细小病毒负荷。与CRC-A和HC组织相比，在CRC组织中发现了更多数量和比例的核心物种。与HC和CRC-A组织相比，CRC组织中黏膜病毒组的多样性显著增加。在物种水平上，CRC组织的黏膜病毒组特征与HC和CRC-A组织的显著不同。与HC相比，Anelloviridae家族的真核病毒及其亚种细小病毒（TTV）在CRC患者中的丰度显著更高。此外，在CRC组中发现肠道固有层中TTV水平升高。与致癌作用相关的TTV的多种病毒功能在CRC组织中得到富集。我们首次揭示，CRC的黏膜病毒群特征是具有更高的多样性和更多的真核病毒。CRC组织中TTV物种的富集表明它们可能在CRC中发挥致癌作用。靶向肠道中的真核病毒可能为CRC的预防和治疗提供新策略。
