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Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Published version of a preprint
Abstract
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, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), 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, all P < 0.0001). Fn was 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, Fn 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 (Fn + Ch + m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC = 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn 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. 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.
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“studies of fecal microbiomes that used either 16s rRNA or shotgun metagenomic sequencing found that F nucleatum to be increased in fecal samples from patients with CRC or adenoma compared with controls (Table 1).15, 18, 35–39”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [39]
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Metadata
- Authors
- Liang, Q., Chiu, J., Chen, Y., Huang, Y., Higashimori, A., Fang, J., Brim, H., Ashktorab, H., Ng, S. C., Ng, S. S. M., Zheng, S., Chan, F. K. L., Sung, J. J. Y., & Yu, J.
- Affiliations
- Chinese University of Hong Kong (HK)
- Shanghai Jiao Tong University (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- 1Institute 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.
- 2Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
- Howard University (US)
- Corresponding author
- Liang, Qiaoyi
- Yu, Jun
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2017-04-13
- Volume
- 23
- Issue
- 8
- Pages
- 2061-2070
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2528647554
- Cited by
- 332
- References
- 31
- Citations by year
- 2026: 28 · 2025: 25 · 2024: 29 · 2023: 37 · 2022: 44 · 2021: 45 · 2020: 41 · 2019: 33 · 2018: 32 · 2017: 16
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China 863 program (2012AA02A506)
- China 973 program (2013CB531401)
- National Nature and Science Foundation of China (81272304)
- The National Key Technology R&D Program (2014BAI09B05)
- Shenzhen Municipal Science and Technology R&D funding (JCYJ20130401151108652)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Health Sciences › Medicine › Microbiology (medical) › Bacterial Identification and Susceptibility Testing
- Keywords
- colorectal cancer, fecal bacteria, non-invasive diagnosis, biomarkers, gut microbiota, Fusobacterium nucleatum, Roseburia intestinalis, metagenomics, fecal immunochemical test, cancer screening
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Feces, Female, Humans, Male, Middle Aged, ROC Curve, Sensitivity and Specificity, Biomarkers, Tumor, Colorectal Neoplasms, Area Under Curve, Real-Time Polymerase Chain Reaction
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