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Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma.

Authors
  • Chen, Feng1
  • Dai, Xudong2
  • Zhou, Chang-Chun3
  • Li, Ke-Xin1
  • Zhang, Yu-Juan1
  • Lou, Xiao-Ying1
  • Zhu, Yuan-Min4
  • Sun, Yan-Lai5
  • Peng, Bao-Xiang6
  • Cui, Wei7
  • 1 Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. , (China)
  • 2 Dept of Clinical Research, Precogify Pharmaceutical Co, Ltd, Beijing, China. , (China)
  • 3 Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. , (China)
  • 4 Department of Gastroenterology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China. , (China)
  • 5 Department of Gastrointestinal Cancer Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. , (China)
  • 6 Clinical Laboratory, Linyi Cancer Hospital, Linyi, China. , (China)
  • 7 Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China [email protected] , (China)
Type
Published Article
Journal
Gut
Publisher
BMJ
Publication Date
Jul 01, 2022
Volume
71
Issue
7
Pages
1315–1325
Identifiers
DOI: 10.1136/gutjnl-2020-323476
PMID: 34462336
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals. Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort. In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93). Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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