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

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

26408641

DOI Digital object identifier for electronic documents.

https://doi.org/10.1136/gutjnl-2015-309800

URI Uniform resource identifier for web resources.

https://gut.bmj.com/content/66/1/70

Authors

Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, Tang L, Zhao H, Stenvang J, Li Y, Wang X, Xu X, Chen N, Wu WK, Al-Aama J, Nielsen HJ, Kiilerich P, Jensen BA, Yau TO, Lan Z, Jia H, Li J, Xiao L, Lam TY, Ng SC, Cheng AS, Wong VW, Chan FK, Xu X, Yang H, Madsen L, Datz C, Tilg H, Wang J, Brünner N, Kristiansen K, Arumugam M, Sung JJ, Wang J

Journal

Gut

Year

2017

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.

Experiment 1

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Curated date: 2023/03/12

Curator: Sophy

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Subjects

Location of subjects: China; Denmark

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine

Group 0 name Corresponds to the control (unexposed) group for case-control studies: control
Group 1 name Corresponds to the case (exposed) group for case-control studies: cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Cohorts C1 and C2 from Hong Kong, China. C1 with colorectal cancer (15 stage I, 21 stage II, 34 stage III and 4 stage IV; median age 67 years; 26 females). C2 with colorectal cancer (4 stage I, 24 stage II, 15 stage III and 4 stage IV; median age 69 years; 22 females). Cohort D from Copenhagen, Denmark. Patients with colorectal cancer (1 stage I, 9 stage II, 5 stage III and 1 stage IV; median age 67.5 years; 6 females).
Group 0 sample size Number of subjects in the control (unexposed) group: 78
Group 1 sample size Number of subjects in the case (exposed) group: 137
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): NA

Lab analysis

Sequencing type: WMS

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

relative abundances

Statistical test

Fisher's Exact Test

Mann-Whitney (Wilcoxon)

PERMANOVA

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: Confounders controlled for: "colonoscopy" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.colonoscopy

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased
Richness Number of species: decreased

Signature 1

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Source: Figure 1A

Description: Differential relative abundance of two CRC-enriched and one control-enriched microbial species consistently identified using three different methods: metagenomic linkage group (MLG), molecular operational taxonomic unit (mOTU) and Integrated Microbial Genome (IMG) database.

Abundance in Group 1: decreased abundance in cohort

NCBI	Links
Eubacterium ventriosum

Revision editor(s): Sophy

Signature 2

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Curated date: 2023/03/12

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Source: Figure 1A

Description: Differential relative abundance of two CRC-enriched and one control-enriched microbial species consistently identified using three different methods: metagenomic linkage group (MLG), molecular operational taxonomic unit (mOTU) and Integrated Microbial Genome (IMG) database.

Abundance in Group 1: increased abundance in cohort

NCBI	Links
Parvimonas micra
Solobacterium moorei
Fusobacterium nucleatum
Peptostreptococcus stomatis

Revision editor(s): Sophy