Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

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. Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two i...

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Bibliographic Details
Published in:Clinical cancer research 2017-04, Vol.23 (8), p.2061-2070
Main Authors: Liang, Qiaoyi, Chiu, Jonathan, Chen, Yingxuan, Huang, Yanqin, Higashimori, Akira, Fang, Jingyuan, Brim, Hassan, Ashktorab, Hassan, Ng, Siew Chien, Ng, Simon Siu Man, Zheng, Shu, Chan, Francis Ka Leung, Sung, Joseph Jao Yiu, Yu, Jun
Format: Article
Language:English
Subjects:
Adult
Aged
Area Under Curve
Bacteria
Bacteroides
Biomarkers
Biomarkers, Tumor - analysis
Cancer
Candidates
Clostridium
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - microbiology
Diagnosis
Diagnostic systems
Experimental design
Feces
Feces - microbiology
Female
Fusobacterium nucleatum
Gastrointestinal Microbiome
Humans
Intestinal microflora
Male
Microbiota
Middle Aged
Performance enhancement
Real-Time Polymerase Chain Reaction
ROC Curve
Sensitivity
Sensitivity and Specificity
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Summary: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. 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. Candidates identified by metagenome sequencing, including ( ), ( ), ( ), ( ), and one undefined species (labeled as ), 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 ( = 0.801-0.934, all < 0.0001). was significantly more abundant in colorectal cancer than controls ( < 0.0001), with AUROC of 0.868 ( < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, discriminated 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 ( + + - ) showed an improved diagnostic ability compared with alone (AUROC = 0.886, < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of alone (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. Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer. .
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-16-1599