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Cited by 312Colorectal Cancer Screening and DetectionGut microbiota and healthGenetic factors in colorectal cancer

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Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia

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Wong, Sunny H, Kwong, Thomas N Y, Chow, Tai-Cheong, Luk, Arthur K C, Dai, Rudin Z W, Nakatsu, Geicho, Lam, Thomas Y T, Zhang, Lin, Wu, Justin C Y, Chan, Francis K L, Ng, Simon S M, Wong, Martin C S, Ng, Siew C, Wu, William K K, Yu, Jun, Sung, Joseph J Y·2017·Gut
DOI 10.1136/gutjnl-2016-312766PMC PMC5530471
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Abstract

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively). Conclusions This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.

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Crossref · 10.1136/gutjnl-2016-312766

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Figure 1 The diagnostic performance of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and their combined test. Sensitivity and area under the receiver-operating characteristic curve (AUC) for diagnosing colorectal cancer (A) and advanced adenoma (B). ***p<0.001.
Figure 1 The diagnostic performance of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and their combined test. Sensitivity and area under the receiver-operating characteristic curve (AUC) for diagnosing colorectal cancer (A) and advanced adenoma (B). ***p<0.001.CC BY-NC · PubMed Central
Figure 2 The diagnostic performance of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and their combined test indicated by the receiver operating characteristic (ROC) curve analysis for colorectal cancer in the discovery (A) and validation (B) cohorts. ***p<0.001. AUC, area under the receiver-operating characteristic curve.
Figure 2 The diagnostic performance of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and their combined test indicated by the receiver operating characteristic (ROC) curve analysis for colorectal cancer in the discovery (A) and validation (B) cohorts. ***p<0.001. AUC, area under the receiver-operating characteristic curve.CC BY-NC · PubMed Central
Figure 3 The colorectal cancer samples detected by faecal immunochemical test (FIT) (red), missed by FIT and detected by marker Fusobacterium nucleatum (Fn) (blue), and missed by both tests (yellow). The dotted lines indicate the threshold of the individual test above which samples are regarded as positive.
Figure 3 The colorectal cancer samples detected by faecal immunochemical test (FIT) (red), missed by FIT and detected by marker Fusobacterium nucleatum (Fn) (blue), and missed by both tests (yellow). The dotted lines indicate the threshold of the individual test above which samples are regarded as positive.CC BY-NC · PubMed Central
Figure 4 The sensitivities of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and the combined test stratified by clinical stage (A), and location of the colorectal cancer (CRC) (B).
Figure 4 The sensitivities of faecal immunochemical test (FIT), marker Fusobacterium nucleatum (Fn) and the combined test stratified by clinical stage (A), and location of the colorectal cancer (CRC) (B).CC BY-NC · PubMed Central

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Metadata

Authors
Wong, S. H., Kwong, T. N. Y., Chow, T.-C., Luk, A. K. C., Dai, R. Z. W., Nakatsu, G., Lam, T. Y. T., Zhang, L., Wu, J. C. Y., Chan, F. K. L., Ng, S. S. M., Wong, M. C. S., Ng, S. C., Wu, W. K. K., Yu, J., & Sung, J. J. Y.
Affiliations
Chinese University of Hong Kong (HK)
Corresponding author
Sung, Joseph J Y
ORCID
Venue
Gut
Publisher
BMJ
Published
2016-10-24
Volume
66
Issue
8
Pages
1441-1448
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2016-312766
PMC
PMC5530471
OpenAlex
W2537258608
Cited by
310
References
32
Citations by year
2026: 28 · 2025: 32 · 2024: 41 · 2023: 40 · 2022: 40 · 2021: 36 · 2020: 34 · 2019: 22 · 2018: 24 · 2017: 13
FWCI
10.61
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Gut (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Croucher Foundation
  • Shenzhen Virtual University Park
  • National Key Research and Development Program of China (2013CB531401)
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
Fusobacterium nucleatum, Peptostreptococcus anaerobius, Parvimonas micra, fecal immunochemical test, colorectal cancer, advanced adenoma, colorectal neoplasia detection, diagnostic sensitivity, non-invasive diagnosis
MeSH terms
Adenocarcinoma, Adenoma, DNA, Bacterial, Feces, Female, Humans, Male, Middle Aged, Occult Blood, Peptostreptococcus, ROC Curve, Biomarkers, Tumor, Colorectal Neoplasms, Fusobacterium nucleatum, Area Under Curve

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