Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer
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AbstractObjective To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.Design We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls.Results Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I{ extendash}II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC.Conclusions We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.
All Author(s) ListYu Jun, Feng Qiang, Wong Sunny Hei, Zhang Dongya, Liang Qiaoyi, Qin Youwen, Tang Longqing, Zhao Hui, Stenvang Jan, Li Yanli, Wang Xiaokai, Xu Xiaoqiang, Chen Ning, Wu William Ka Kei, Al-Aama Jumana, Nielsen Hans J{ø}rgen, Kiilerich Pia, Jensen Benjamin Anderschou Holbech, Yau Tung On, Lan Zhou, Jia Huijue, Li Junhua, Xiao Liang, Lam Thomas Yuen Tung, Ng Siew Chien, Cheng Alfred Sze-Lok, Wong Vincent Wai-Sun, Chan Francis Ka Leung, Xu Xun, Yang Huanming, Madsen Lise, Datz Christian, Tilg Herbert, Wang Jian, Brünner Nils, Kristiansen Karsten, Arumugam Manimozhiyan, Sung Joseph Jao-Yiu, Wang Jun
Journal nameGut
Volume Number66
Issue Number1
PublisherBMJ Publishing Group
Pages70 - 78
LanguagesEnglish-United States

Last updated on 2021-22-09 at 00:52