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

• Published in: Gut Vol. 66; no. 8; pp. 1441 - 1448
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2017; BMJ Publishing Group
• Series: Original article
• Subjects: Abundance; Adenocarcinoma - diagnosis; Adenoma; Adenoma - diagnosis; Area Under Curve; Biomarkers; Biomarkers, Tumor - analysis; Colon; Colonoscopy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Deoxyribonucleic acid; DNA; DNA, Bacterial - analysis; Feces - microbiology; Female; Fusobacterium nucleatum; Gastroenterology; Genomes; Humans; Male; Medical screening; Middle Aged; Occult Blood; Peptostreptococcus; Quantitation; ROC Curve; Tumors; Asia; COLORECTAL CANCER; COLONIC MICROFLORA; COLORECTAL ADENOMAS; COLORECTAL CANCER SCREENING
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2016-312766

ObjectiveThere 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.DesignWe 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.ResultsThe 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).ConclusionsThis 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.