title: Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer.
abstract: Purpose:Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design:Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results:Candidates identified by metagenome sequencing, includingFusobacterium nucleatum(Fn),Bacteroides clarus(Bc),Roseburia intestinalis(Ri),Clostridium hathewayi(Ch), and one undefined species (labeled asm7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r= 0.801-0.934, allP< 0.0001).Fnwas significantly more abundant in colorectal cancer than controls (P< 0.0001), with AUROC of 0.868 (P< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,Fndiscriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn+Ch+m7-Bc) showed an improved diagnostic ability compared withFnalone (AUROC = 0.886,P< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances ofFnalone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions:Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.Clin Cancer Res; 23(8); 2061-70. ©2016 AACR.
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China. junyu@cuhk.edu.hk JessieQY@cuhk.edu.hk.
authors.forename: Qiaoyi
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chiu
authors.affiliation: Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yingxuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.|Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Higashimori
authors.affiliation: Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.affiliation: Cancer Center and Pathology Department, Howard University College of Medicine, Washington, DC.
authors.forename: Hassan
authors.initials: H
authors.lastname: Brim
authors.affiliation: Cancer Center and Pathology Department, Howard University College of Medicine, Washington, DC.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Siew Chien
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Simon Siu Man
authors.initials: SSM
authors.lastname: Ng
authors.affiliation: Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Francis Ka Leung
authors.initials: FKL
authors.lastname: Chan
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Joseph Jao Yiu
authors.initials: JJY
authors.lastname: Sung
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China. junyu@cuhk.edu.hk JessieQY@cuhk.edu.hk.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor