A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer

Jessie Qiaoyi Liang, Tong Li, Geicho Nakatsu, Ying-Xuan Chen, Tung On Yau, Eagle Chu, Sunny Wong, Chun Ho Szeto, Siew C Ng, Francis K L Chan, Jing-Yuan Fang, Joseph J Y Sung, Jun Yu

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

OBJECTIVE: There is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.

DESIGN: This study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.

RESULTS: Metagenomic analysis identified 'm3' from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal m3 may perform better than Fn in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) m3=0.675 vs Fn=0.620, p=0.09), while Fn performed better in diagnosing CRC (AUROCs Fn=0.862 vs m3=0.741, p<0.0001). At 78.5% specificity, m3 and Fn showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), m3 performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by m3 (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of m3 for advanced adenoma to 56.8%. The combination of m3 with Fn, Ch, Bacteroides clarus and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%).

CONCLUSION: This study identifies a novel bacterial marker m3 for the non-invasive diagnosis of colorectal adenoma.

Original languageEnglish
Pages (from-to)1248-1257
Number of pages10
JournalGut
Volume69
Issue number7
Early online date27 Nov 2019
DOIs
Publication statusPrint publication - 6 Jun 2020
Externally publishedYes

Keywords

  • Adenoma/diagnosis
  • Biomarkers, Tumor/analysis
  • Case-Control Studies
  • Clostridiales/metabolism
  • Colorectal Neoplasms/diagnosis
  • Feces/chemistry
  • Female
  • Humans
  • Male
  • Metagenomics
  • Middle Aged
  • Polymerase Chain Reaction
  • Sensitivity and Specificity
  • colorectal adenomas
  • colonic bacteria
  • colorectal cancer screening

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