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Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study
Cancer Letters ( IF 9.1 ) Pub Date : 2020-11-27 , DOI: 10.1016/j.canlet.2020.11.030
Qian Xiao , Wei Lu , Xiangxing Kong , Yang W. Shao , Yeting Hu , Ao Wang , Hua Bao , Ran Cao , Kaihua Liu , Xiaonan Wang , Xue Wu , Shu Zheng , Ying Yuan , Kefeng Ding

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.



中文翻译:

大肠癌和腺瘤中循环细菌DNA的改变:概念验证研究

肠道菌群与结肠直肠肿瘤密切相关。尽管大多数宏基因组学研究都使用粪便样本,但结直肠肿瘤患者中的循环细菌DNA仍未开发。这项概念验证研究旨在表征结直肠肿瘤患者中循环细菌DNA的变化。我们对25名大肠癌(CRC),10名大肠腺瘤(CRA)和22名健康对照(HC)的血浆样本进行了WGS检测。通过去除宿主基因组并将读数映射到细菌基因组中来测量细菌相对丰度。通过多样性分析,我们发现血浆样品比粪便样品需要更少的样品量才能达到饱和,并且与CRC / CRA患者相比,HC中的物种多样性略高。循环中的细菌DNA大多数来自细菌属,通常与胃肠道和口腔有关。通过差异分析,在CRC患者和HC之间共鉴定了127个重要物种,在此基础上选择了具有最高预测能力的28个物种,并显示出对CRC / CRA和HC的初步区分的希望。在CRA患者中,所选的28个物种的相对丰度比HC患者更接近于CRC患者。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的倍数变化之间存在中等正相关。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。结论,

更新日期:2020-11-27
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