TY - JOUR
T1 - Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer
AU - Yu, Jun
AU - Feng, Qiang
AU - Wong, Sunny Hei
AU - Zhang, Dongya
AU - Liang, Qiao Yi
AU - Qin, Youwen
AU - Tang, Longqing
AU - Zhao, Hui
AU - Stenvang, Jan
AU - Li, Yanli
AU - Wang, Xiaokai
AU - Xu, Xiaoqiang
AU - Chen, Ning
AU - Wu, William Ka Kei
AU - Al-Aama, Jumana
AU - Nielsen, Hans Jørgen
AU - Kiilerich, Pia
AU - Jensen, Benjamin Anderschou Holbech
AU - Yau, Tung On
AU - Lan, Zhou
AU - Jia, Huijue
AU - Li, Junhua
AU - Xiao, Liang
AU - Lam, Thomas Yuen Tung
AU - Ng, Siew Chien
AU - Cheng, Alfred Sze-Lok
AU - Wong, Vincent Wai-Sun
AU - Chan, Francis Ka Leung
AU - Xu, Xun
AU - Yang, Huanming
AU - Madsen, Lise
AU - Datz, Christian
AU - Tilg, Herbert
AU - Wang, Jian
AU - Brünner, Nils
AU - Kristiansen, Karsten
AU - Arumugam, Manimozhiyan
AU - Sung, Joseph Jao-Yiu
AU - Wang, Jun
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PY - 2017
Y1 - 2017
N2 - 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.
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.
U2 - 10.1136/gutjnl-2015-309800
DO - 10.1136/gutjnl-2015-309800
M3 - Journal article
C2 - 26408641
VL - 66
SP - 70
EP - 78
JO - Gut
JF - Gut
SN - 0017-5749
ER -