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

Open access
Yu, Jun, Feng, Qiang, Wong, Sunny Hei, Zhang, Dongya, Liang, Qiao yi, 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 Jørgen, 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·2017·Gut

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.

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Research works printed but not linked: 2

  1. Ferlay, 2013, GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. IARC CancerBase
  2. Yoshioka, 2005, Binding of Actinobacillus actinomycetemcomitans lipopolysaccharides to Peptostreptococcus micros stimulates tumor necrosis factor alpha production by macrophage-like cells, Oral Microbiol Immunol, 20, 118, 10.1111/j.1399-302X.2004.00204.x · doi:10.1111/j.1399-302x.2004.00204.x

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Metadata

Authors
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., Lan, Z., Jia, H., Li, J., Xiao, L., Lam, T. Y. T., Ng, S. C., Cheng, A. S.-L., Wong, V. W.-S., Chan, F. K. L., Xu, X., Yang, H., Madsen, L., Datz, C., Tilg, H., Wang, J., Brünner, N., Kristiansen, K., Arumugam, M., Sung, J. J.-Y., & Wang, J.
Venue
Gut
Publisher
BMJ
Published
2015-09-25
Volume
66
Issue
1
Pages
70-78
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
OpenAlex
W2178425989
Cited by
1,253
References
44
FWCI
15.31
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. https://app.cochat.ai/papers/10.1136/gutjnl-2015-309800
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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. https://doi.org/10.1136/gutjnl-2015-309800

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.