Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, Ontario, M5G 1L7, Canada; School of Public Health, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Cancer Lett. 2021 Feb 28;499:201-208. doi: 10.1016/j.canlet.2020.11.030. Epub 2020 Nov 27.
The gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating bacterial DNA in colorectal neoplasia patients remained unexplored. This proof-of-concept study aims to characterize alterations of circulating bacterial DNA in colorectal neoplasia patients. We performed WGS of plasma samples from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). Bacterial relative abundance was measured by removing the host genome and mapping reads into bacterial genomes. By diversity analysis, we found plasma samples required less sample size to approach saturation than fecal samples, and species diversity in HC was slightly higher compared with CRC/CRA patients. The majority of circulating bacterial DNA came from bacterial genera which commonly associated with gastrointestine and oral tract. By differential analysis, a total of 127 significant species between CRC patients and HC were identified, on which basis 28 species with top predictive ability were selected and showed promise in preliminary discrimination between CRC/CRA and HC. In CRA patients, relative abundance of the selected 28 species more closely resembled those in CRC patients than HC. By comparing with fecal metagenomics studies, we found there was moderate positive correlation between fold changes of the overlapped fecal and circulating bacterial DNA. Finally, species correlation analysis revealed that CRC and HC displayed distinct patterns of species association. In conclusion, this study demonstrated alterations of circulating bacterial DNA in colorectal neoplasia patients, which had the potential to become non-invasive biomarkers for colorectal neoplasia screening and early diagnosis.
肠道微生物群与结直肠肿瘤密切相关。虽然大多数宏基因组学研究都使用粪便样本，但结直肠肿瘤患者循环细菌 DNA 仍未得到探索。本概念验证研究旨在描述结直肠肿瘤患者循环细菌 DNA 的变化。我们对 25 名结直肠癌 (CRC) 患者、10 名结直肠腺瘤 (CRA) 患者和 22 名健康对照 (HC) 的血浆样本进行了 WGS 分析。通过去除宿主基因组并将读取映射到细菌基因组，测量细菌相对丰度。通过多样性分析，我们发现与粪便样本相比，血浆样本需要更少的样本量即可达到饱和，并且 HC 中的物种多样性略高于 CRC/CRA 患者。大多数循环细菌 DNA 来自与胃肠道和口腔密切相关的细菌属。通过差异分析，在 CRC 患者和 HC 之间总共鉴定出 127 个显著的物种，在此基础上，选择了具有最高预测能力的 28 个物种，并在初步区分 CRC/CRA 和 HC 方面显示出了潜力。在 CRA 患者中，所选 28 个物种的相对丰度更接近 CRC 患者而不是 HC。通过与粪便宏基因组学研究进行比较，我们发现重叠粪便和循环细菌 DNA 的变化之间存在中度正相关。最后，物种相关性分析表明 CRC 和 HC 显示出不同的物种关联模式。总之，本研究表明结直肠肿瘤患者循环细菌 DNA 发生了变化，有潜力成为结直肠肿瘤筛查和早期诊断的非侵入性生物标志物。
