Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Jun Yu; Qiang Feng; Sunny Hei Wong; Dongya Zhang; Qiao Yi Liang; Youwen Qin; Longqing Tang; Hui Zhao; Jan Stenvang; Yanli Li; Xiaokai Wang; Xiaoqiang Xu; Ning Chen; William Ka Kei Wu; Jumana Al-Aama; Hans Jørgen Nielsen; Pia Kiilerich; Benjamin Anderschou Holbech Jensen; Tung On Yau; Zhou Lan; Huijue Jia; Junhua Li; Liang Xiao; Thomas Yuen Tung Lam; Siew Chien Ng; Alfred Sze-Lok Cheng; Vincent Wai-Sun Wong; Francis Ka Leung Chan; Xun Xu; Huanming Yang; Lise Madsen; Christian Datz; Herbert Tilg; Jian Wang; Nils Brünner; Karsten Kristiansen; Manimozhiyan Arumugam; Joseph Jao-Yiu Sung; Jun Wang

doi:10.1136/gutjnl-2015-309800

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Jun Yu, Qiang Feng, Sunny Hei Wong, Dongya Zhang, Qiao Yi Liang, Youwen Qin, Longqing Tang, Hui Zhao, Jan Stenvang, Yanli Li, Xiaokai Wang, Xiaoqiang Xu, Ning Chen, William Ka Kei Wu, Jumana Al-Aama, Hans Jørgen Nielsen, Pia Kiilerich, Benjamin Anderschou Holbech Jensen, Tung On Yau, Zhou LanHuijue Jia, Junhua Li, Liang Xiao, Thomas Yuen Tung Lam, Siew Chien Ng, Alfred Sze-Lok Cheng, Vincent Wai-Sun Wong, Francis Ka Leung Chan, Xun Xu, Huanming Yang, Lise Madsen, Christian Datz, Herbert Tilg, Jian Wang, Nils Brünner, Karsten Kristiansen, Manimozhiyan Arumugam, Joseph Jao-Yiu Sung, Jun Wang

309 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Gut
Volume	66
Pages (from-to)	70-78
Number of pages	9
ISSN	0017-5749
DOIs	https://doi.org/10.1136/gutjnl-2015-309800
Publication status	Published - 2017

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Yu, J., Feng, Q., Wong, S. H., Zhang, D., Liang, Q. Y., Qin, Y., Tang, L., Zhao, H., Stenvang, J., Li, Y., Wang, X., Xu, X., Chen, N., Wu, W. K. K., Al-Aama, J., Nielsen, H. J., Kiilerich, P., Jensen, B. A. H., Yau, T. O., ... Wang, J. (2017). Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut, 66, 70-78. https://doi.org/10.1136/gutjnl-2015-309800

Yu, J, Feng, Q, Wong, SH, Zhang, D, Liang, QY, Qin, Y, Tang, L, Zhao, H, Stenvang, J, Li, Y, Wang, X, Xu, X, Chen, N, Wu, WKK, Al-Aama, J, Nielsen, HJ, Kiilerich, P, Jensen, BAH, Yau, TO, Lan, Z, Jia, H, Li, J, Xiao, L, Lam, TYT, Ng, SC, Cheng, AS-L, Wong, VW-S, Chan, FKL, Xu, X, Yang, H, Madsen, L, Datz, C, Tilg, H, Wang, J, Brünner, N , Kristiansen, K , Arumugam, M, Sung, JJ-Y & Wang, J 2017, 'Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer', Gut, vol. 66, pp. 70-78. https://doi.org/10.1136/gutjnl-2015-309800

@article{a8af7a72254e4201954f7b72b4e7f9b9,

title = "Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer",

abstract = "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.",

author = "Jun Yu and Qiang Feng and Wong, {Sunny Hei} and Dongya Zhang and Liang, {Qiao Yi} and Youwen Qin and Longqing Tang and Hui Zhao and Jan Stenvang and Yanli Li and Xiaokai Wang and Xiaoqiang Xu and Ning Chen and Wu, {William Ka Kei} and Jumana Al-Aama and Nielsen, {Hans J{\o}rgen} and Pia Kiilerich and Jensen, {Benjamin Anderschou Holbech} and Yau, {Tung On} and Zhou Lan and Huijue Jia and Junhua Li and Liang Xiao and Lam, {Thomas Yuen Tung} and Ng, {Siew Chien} and Cheng, {Alfred Sze-Lok} and Wong, {Vincent Wai-Sun} and Chan, {Francis Ka Leung} and Xun Xu and Huanming Yang and Lise Madsen and Christian Datz and Herbert Tilg and Jian Wang and Nils Br{\"u}nner and Karsten Kristiansen and Manimozhiyan Arumugam and Sung, {Joseph Jao-Yiu} and Jun Wang",

note = "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.",

year = "2017",

doi = "10.1136/gutjnl-2015-309800",

language = "English",

volume = "66",

pages = "70--78",

journal = "Gut",

issn = "0017-5749",

publisher = "B M J Group",

}

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

SN - 0017-5749

VL - 66

SP - 70

EP - 78

JO - Gut

JF - Gut

ER -

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Abstract

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