Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study
Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study
复制标题
结直肠癌和腺瘤中循环细菌 DNA 的改变：概念验证研究
DOI：
10.1016/j.canlet.2020.11.030
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发表时间：
2021-02-28
期刊：
影响因子：
9.7
通讯作者：
Ding, Kefeng
中科院分区：
文献类型：
--
作者：
Xiao, Qian;Lu, Wei;Ding, Kefeng
肠道菌群与结直肠肿瘤密切相关。虽然大多数宏基因组学研究利用了粪便样本，但结肠直肠癌肿瘤患者的循环细菌DNA仍未被探索。这项概念验证性研究旨在描述结直肠肿瘤患者循环细菌DNA的改变。我们对25例结直肠癌（CRC）患者、10例结直肠腺瘤（CRA）患者和22例健康对照（HC）的血浆样本进行了WGS检测。细菌的相对丰度是通过去除宿主基因组并将读数定位到细菌基因组来测量的。通过多样性分析，我们发现血浆样本比粪便样本需要更少的样本量来接近饱和，HC患者的物种多样性略高于CRC/CRA患者。大多数循环细菌DNA来自通常与胃肠道和口腔有关的细菌属。通过差异分析，共鉴定出127个CRC患者与HC之间的显著物种，在此基础上筛选出28个预测能力最强的物种，有望初步区分CRC/CRA与HC。在CRA患者中，所选28个物种的相对丰度与CRC患者的相对丰度更接近。通过与粪便宏基因组学研究的比较，我们发现重叠粪便的折叠变化与循环细菌DNA之间存在中度正相关。物种相关分析表明，CRC和HC表现出不同的物种关联模式。总之，本研究证实了结直肠肿瘤患者循环细菌DNA的改变，这有可能成为结直肠肿瘤筛查和早期诊断的非侵入性生物标志物。
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.