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Gut. 2017 Jan;66(1):70-78. doi: 10.1136/gutjnl-2015-309800. Epub 2015 Sep 25.

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

Author information

1
Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
2
BGI-Shenzhen, Shenzhen, China.
3
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
4
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
6
Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
7
National Institute of Nutrition and Seafood Research, Bergen, Norway.
8
Department of Internal Medicine, Hospital Oberndorf, Q3 Teaching Hospital of the Paracelsus Private University of Salzburg, Oberndorf, Austria.
9
First Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
10
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
11
Macau University of Science and Technology, Macau, China.

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.

KEYWORDS:

BACTERIAL INTERACTIONS; COLONIC MICROFLORA; COLORECTAL CANCER

PMID:
26408641
DOI:
10.1136/gutjnl-2015-309800
[Indexed for MEDLINE]

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