PT  - JOURNAL ARTICLE
AU  - Jun Yu
AU  - Qiang Feng
AU  - Sunny Hei Wong
AU  - Dongya Zhang
AU  - Qiao yi Liang
AU  - Youwen Qin
AU  - Longqing Tang
AU  - Hui Zhao
AU  - Jan Stenvang
AU  - Yanli Li
AU  - Xiaokai Wang
AU  - Xiaoqiang Xu
AU  - Ning Chen
AU  - William Ka Kei Wu
AU  - Jumana Al-Aama
AU  - Hans Jørgen Nielsen
AU  - Pia Kiilerich
AU  - Benjamin Anderschou Holbech Jensen
AU  - Tung On Yau
AU  - Zhou Lan
AU  - Huijue Jia
AU  - Junhua Li
AU  - Liang Xiao
AU  - Thomas Yuen Tung Lam
AU  - Siew Chien Ng
AU  - Alfred Sze-Lok Cheng
AU  - Vincent Wai-Sun Wong
AU  - Francis Ka Leung Chan
AU  - Xun Xu
AU  - Huanming Yang
AU  - Lise Madsen
AU  - Christian Datz
AU  - Herbert Tilg
AU  - Jian Wang
AU  - Nils Brünner
AU  - Karsten Kristiansen
AU  - Manimozhiyan Arumugam
AU  - Joseph Jao-Yiu Sung
AU  - Jun Wang
TI  - Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer
AID  - 10.1136/gutjnl-2015-309800
DP  - 2017 Jan 01
TA  - Gut
PG  - 70--78
VI  - 66
IP  - 1
4099  - http://gut.bmj.com/content/66/1/70.short
4100  - http://gut.bmj.com/content/66/1/70.full
SO  - Gut2017 Jan 01; 66
AB  - Objective 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–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.