Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Jun Yu, Qiang Feng, Sunny Hei Wong, Dongya Zhang, Qiao Yi Liang, Youwen Qin, Longqing Tang, Hui Zhao, Jan Stenvang, Yanli Li, Xiaokai Wang, Xiaoqiang Xu, Ning Chen, William Ka Kei Wu, Jumana Al-Aama, Hans Jørgen Nielsen, Pia Kiilerich, Benjamin Anderschou Holbech Jensen, Tung On Yau, Zhou LanHuijue Jia, Junhua Li, Liang Xiao, Thomas Yuen Tung Lam, Siew Chien Ng, Alfred Sze-Lok Cheng, Vincent Wai-Sun Wong, Francis Ka Leung Chan, Xun Xu, Huanming Yang, Lise Madsen, Christian Datz, Herbert Tilg, Jian Wang, Nils Brünner, Karsten Kristiansen, Manimozhiyan Arumugam, Joseph Jao-Yiu Sung, Jun Wang

Research output: Contribution to journalArticlepeer-review

492 Citations (Scopus)

Abstract

OBJECTIVE: To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.

DESIGN: We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls.

RESULTS: Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC.

CONCLUSIONS: We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalGut
Volume66
Issue number1
DOIs
Publication statusPrint publication - Jan 2017
Externally publishedYes

Keywords

  • Aged
  • Area Under Curve
  • Austria
  • Biomarkers, Tumor
  • Case-Control Studies
  • China
  • Cohort Studies
  • Colorectal Neoplasms/complications
  • Denmark
  • Dysbiosis/complications
  • Feces/microbiology
  • Female
  • Firmicutes/isolation & purification
  • France
  • Fusobacterium nucleatum/isolation & purification
  • Gastrointestinal Microbiome/genetics
  • Genome-Wide Association Study
  • Humans
  • Male
  • Metagenomics
  • Middle Aged
  • Peptostreptococcus/isolation & purification
  • ROC Curve

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