Article Text

Download PDFPDF

Original article
Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia
  1. Sunny H Wong1,2,3,
  2. Thomas N Y Kwong1,2,
  3. Tai-Cheong Chow1,2,
  4. Arthur K C Luk1,2,
  5. Rudin Z W Dai1,2,
  6. Geicho Nakatsu1,2,
  7. Thomas Y T Lam1,2,
  8. Lin Zhang1,4,
  9. Justin C Y Wu1,2,
  10. Francis K L Chan1,2,
  11. Simon S M Ng1,5,
  12. Martin C S Wong1,6,
  13. Siew C Ng1,2,
  14. William K K Wu1,2,3,4,
  15. Jun Yu1,2,3,
  16. Joseph J Y Sung1,2,3
  1. 1 State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Institute of Digestive Disease, Hong Kong, Hong Kong
  2. 2 Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  3. 3 CUHK Shenzhen Research Institute, Shenzhen, China
  4. 4 Faculty of Medicine, Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  5. 5 Faculty of Medicine, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  6. 6 Faculty of Medicine, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  1. Correspondence to Professor Joseph J Y Sung, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong; jjysung{at}cuhk.edu.hk

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

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

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.