Re-purposing 16S rRNA gene sequence data from within case paired tumor biopsy and tumor-adjacent biopsy or fecal samples to identify microbial markers for colorectal cancer

Study information

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study design

meta-analysis

Citation

PMID PubMed identifier for scientific articles.

30412600

DOI Digital object identifier for electronic documents.

10.1371/journal.pone.0207002

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226189/

Authors

Shah MS, DeSantis T, Yamal JM, Weir T, Ryan EP, Cope JL, Hollister EB

Journal

PloS one

Year

2018

Microbes colonizing colorectal cancer (CRC) tumors have the potential to affect disease, and vice-versa. The manner in which they differ from microbes in physically adjacent tissue or stool within the case in terms of both, taxonomy and biological activity remains unclear. In this study, we systematically analyzed previously published 16S rRNA sequence data from CRC patients with matched tumor:tumor-adjacent biopsies (n = 294 pairs, n = 588 biospecimens) and matched tumor biopsy:fecal pairs (n = 42 pairs, n = 84 biospecimens). Procrustes analyses, random effects regression, random forest (RF) modeling, and inferred functional pathway analyses were conducted to assess community similarity and microbial diversity across heterogeneous patient groups and studies. Our results corroborate previously reported association of increased Fusobacterium with tumor biopsies. Parvimonas and Streptococcus abundances were also elevated while Faecalibacterium and Ruminococcaceae abundances decreased in tumors relative to tumor-adjacent biopsies and stool samples from the same case. With the exception of these limited taxa, the majority of findings from individual studies were not confirmed by other 16S rRNA gene-based datasets. RF models comparing tumor and tumor-adjacent specimens yielded an area under curve (AUC) of 64.3%, and models of tumor biopsies versus fecal specimens exhibited an AUC of 82.5%. Although some taxa were shared between fecal and tumor samples, their relative abundances varied substantially. Inferred functional analysis identified potential differences in branched amino acid and lipid metabolism. Microbial markers that reliably occur in tumor tissue can have implications for microbiome based and microbiome targeting therapeutics for CRC.

Experiment 1

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Curated date: 2022/01/03

Curator: Itslanapark

Revision editor(s): WikiWorks, Itslanapark, Scholastica, Aleru Divine, KateRasheed

Subjects

Location of subjects

United States of America

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

Colorectal mucosa , Feces Colorectal mucosa,colorectal mucosa,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

Healthy tumor-adjacent biopsy

Group 1 name Corresponds to the case (exposed) group for case-control studies

CRC tumor biopsy

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Colorectal tumor tissues

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

294

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

294

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

1 - 3 months

Lab analysis

Sequencing type

16S

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, Roche454

Statistical Analysis

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

raw counts

Statistical test

DESeq2

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: "paired design" 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.paired design, Confounders controlled for: "host genetics" 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.host genetics, Confounders controlled for: "expression" 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.expression, Confounders controlled for: "immune response" 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.immune response

Signature 1

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Curated date: 2024/03/11

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Source: Figure 2A, Result text

Description: Pairwise differences in CRC tumor vs. healthy adjacent tissue. Boxplots indicate the distribution of the relative abundances of various taxa and corresponding lines connect paired samples, depicting the direction of change in relative abundance of statistically significantly different families between CRC tumor biopsy samples and adjacent non-affected tissue microbiome(n = 294 pairs, 588 samples)

Abundance in Group 1: increased abundance in CRC tumor biopsy

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Fusobacterium
Leptotrichia
Parvimonas
Peptostreptococcus
Streptococcus
Actinomycetota

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Signature 2

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Source: Figure 2A, Result text

Description: Description: Pairwise differences in CRC tumor vs. healthy adjacent tissue. Boxplots indicate the distribution of the relative abundances of various taxa and corresponding lines connect paired samples, depicting the direction of change in relative abundance of statistically significantly different families between CRC tumor biopsy samples and adjacent non-affected tissue microbiome(n = 294 pairs, 588 samples)

Abundance in Group 1: decreased abundance in CRC tumor biopsy

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Dorea
Faecalibacterium
Parabacteroides
unclassified Rikenellaceae
Oscillospiraceae

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Experiment 2

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Curated date: 2024/03/11

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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Feces , Colorectal mucosa 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,Colorectal mucosa,colorectal mucosa

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

Tumor biopsy

Group 1 name Corresponds to the case (exposed) group for case-control studies

Fecal samples

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Fecal samples from the same colorectal case

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

42

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

42

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2024/03/11

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Source: Figure 2B, Result text

Description: Pairwise differences in tumor biopsy fecal samples. Boxplots indicate the distribution of the relative abundances of various taxa and corresponding lines connect paired samples, depicting the direction of change in relative abundance of statistically significantly different families between CRC tumor biopsy and fecal samples (n = 42 pairs, 84 samples)

Abundance in Group 1: increased abundance in Fecal samples

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Roseburia
Blautia
Bifidobacterium

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Source: Figure 2B, Result text

Description: Pairwise differences in tumor biopsy fecal samples. Boxplots indicate the distribution of the relative abundances of various taxa and corresponding lines connect paired samples, depicting the direction of change in relative abundance of statistically significantly different families between CRC tumor biopsy and fecal samples (n = 42 pairs, 84 samples)

Abundance in Group 1: decreased abundance in Fecal samples

NCBI	Quality Control	Links
Fusobacterium
Streptococcus
Prevotella
Staphylococcus

Revision editor(s): Scholastica, WikiWorks