title: Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer.
abstract: To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Sunny Hei
authors.initials: SH
authors.lastname: Wong
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Qiao Yi
authors.initials: QY
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Qin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Longqing
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Stenvang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaokai
authors.initials: X
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jumana
authors.initials: J
authors.lastname: Al-Aama
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Nielsen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Kiilerich
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benjamin Anderschou Holbech
authors.initials: BA
authors.lastname: Jensen
authors.affiliation: 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.
authors.forename: Tung On
authors.initials: TO
authors.lastname: Yau
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lan
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huijue
authors.initials: H
authors.lastname: Jia
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Thomas Yuen Tung
authors.initials: TY
authors.lastname: Lam
authors.affiliation: 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.
authors.forename: Siew Chien
authors.initials: SC
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Alfred Sze-Lok
authors.initials: AS
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Francis Ka Leung
authors.initials: FK
authors.lastname: Chan
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Q3 Teaching Hospital of the Paracelsus Private University of Salzburg, Oberndorf, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.affiliation: First Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Manimozhiyan
authors.initials: M
authors.lastname: Arumugam
authors.affiliation: 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.
authors.forename: Joseph Jao-Yiu
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.|Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.|Macau University of Science and Technology, Macau, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001317:Austria; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000150:complications / Q000175:diagnosis*; D003718:Denmark; D064806:Dysbiosis / Q000150:complications / Q000382:microbiology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000068536:Bacillota / Q000302:isolation & purification; D005602:France; D016967:Fusobacterium nucleatum / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D010462:Peptostreptococcus / Q000302:isolation & purification; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor
keywords: BACTERIAL INTERACTIONS; COLONIC MICROFLORA; COLORECTAL CANCER