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

Sunny H Wong, Thomas N Y Kwong, Tai-Cheong Chow, Arthur K C Luk, Rudin Z W Dai, Geicho Nakatsu, Thomas Y T Lam, Lin Zhang, Justin C Y Wu, Francis K L Chan, Simon S M Ng, Martin C S Wong, Siew C Ng, William K K Wu, Jun Yu, Joseph J Y Sung, Sunny H Wong, Thomas N Y Kwong, Tai-Cheong Chow, Arthur K C Luk, Rudin Z W Dai, Geicho Nakatsu, Thomas Y T Lam, Lin Zhang, Justin C Y Wu, Francis K L Chan, Simon S M Ng, Martin C S Wong, Siew C Ng, William K K Wu, Jun Yu, Joseph J Y Sung

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.

Keywords: COLONIC MICROFLORA; COLORECTAL ADENOMAS; COLORECTAL CANCER; COLORECTAL CANCER SCREENING.

Conflict of interest statement

Competing interests: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
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 2
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 3
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 4
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).

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Source: PubMed

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