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

Study information

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study design

cross-sectional observational, not 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

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

Keywords:

BACTERIAL INTERACTIONS, COLONIC MICROFLORA, COLORECTAL CANCER

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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Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/12

Curator: Sophy

Revision editor(s): Sophy, Claregrieve1, Atrayees

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: 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,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,Colorectal cancer

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: Colorectal cancer patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with colorectal cancer.

Group 0 sample size Number of subjects in the control (unexposed) group: 54

Group 1 sample size Number of subjects in the case (exposed) group: 74

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

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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: Mann-Whitney (Wilcoxon)

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

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

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: Supplementary Table 8

Description: Differential abundance of IMG, mOTU and MLG species associated with CRC patients and controls.

Abundance in Group 1: increased abundance in Colorectal cancer patients

NCBI	Quality Control	Links
Alistipes indistinctus
Bacteroides fragilis
Beggiatoa sp. PS
Burkholderia mallei
Cloacibacillus evryensis
Clostridiales bacterium 1_7_47FAA
Clostridium sp. HGF2
Coprobacillus sp. 3_3_56FAA
Crenothrix polyspora
Desulfovibrio sp. 6_1_46AFAA
Dorea formicigenerans
Filifactor alocis
Fusobacterium necrophorum
Fusobacterium nucleatum
Fusobacterium sp. oral taxon 370 str. F0437
Fusobacterium varium
Gemella morbillorum
Hungatella hathewayi
Lachnospiraceae bacterium 3_1_46FAA
Lachnospiraceae bacterium 3_1_57FAA_CT1
Lachnospiraceae bacterium 5_1_57FAA
Lachnospiraceae bacterium 8_1_57FAA
Leptotrichia buccalis
Malassezia globosa
Paracoccus denitrificans
Parvimonas micra
Parvimonas sp. oral taxon 110
Parvimonas sp. oral taxon 393
Peptoniphilus indolicus
Peptostreptococcus anaerobius
Peptostreptococcus stomatis
Prevotella intermedia
Solobacterium moorei
Streptobacillus moniliformis
Streptococcus constellatus
Streptococcus dysgalactiae
Streptococcus equi
Streptococcus equinus
Streptococcus pseudoporcinus
Subdoligranulum sp. 4_3_54A2FAA
Sulfurovum sp. SCGC AAA036-O23
Synergistes sp. 3_1_syn1
[Clostridium] symbiosum

Revision editor(s): Sophy, Atrayees

Signature 2

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Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/12

Curator: Sophy

Revision editor(s): Sophy, Atrayees

Source: Supplementary Table 8

Description: Differential abundance of IMG, mOTU and MLG species associated with CRC patients and controls.

Abundance in Group 1: decreased abundance in Colorectal cancer patients

NCBI	Quality Control	Links
Burkholderiales bacterium 1_1_47
Eubacterium ventriosum
Adhaeribacter aquaticus
Coprococcus sp. ART55/1
butyrate-producing bacterium SS3/4
Haemophilus parainfluenzae
Holdemanella biformis
Faecalibacterium prausnitzii
[Ruminococcus] torques
Klebsiella pneumoniae
Lachnospira eligens
Bacteroides clarus
Blautia obeum
Clostridium sp. L2-50
Roseburia intestinalis
Agathobacter rectalis

Revision editor(s): Sophy, Atrayees