Article Text
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.
- COLORECTAL CANCER
- COLORECTAL ADENOMAS
- COLORECTAL CANCER SCREENING
- COLONIC MICROFLORA
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Footnotes
SHW and TNYK contributed equally.
Contributors Study concept and design: SHW, WKKW, JJYS, JY; acquisition of data: TNYK, T-CC, AKCL; analysis and interpretation of data: SHW, TNYK, RZWD, GN; drafting of the manuscript: SHW; critical revision of the manuscript for important intellectual content: JJYS, JY, WKKW, JCYW, FKLC, SSMN, MCSW, SCN, TYTL, LZ; statistical analysis: SHW, RZWD, GN.
Funding This project was supported by the National Basic Research Program of China (973 Program, 2013CB531401), National Key Technology R&D Program (2014BAI09B05), the Shenzhen Virtual University Park Support Scheme, the Shenzhen Science and Technology Programme, and the Croucher Foundation. SHW is supported by the Croucher Foundation. The study sponsor has no role in the study design, data collection, analysis and interpretation of the data.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.