Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction

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Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Liu J., Huang X., Chen C., Wang Z., Huang Z., Qin M., He F., Tang B., Long C., Hu H., Pan S., Wu J., Tang W.
Journal
Journal of translational medicine
Year
2023
Keywords:
16S rRNA, Colorectal cancer, Immune infiltration, Intestinal microbiome, Staging prediction
OBJECTIVE: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. METHOD: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. RESULT: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. CONCLUSIONS: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

Experiment 1


Needs review

Curated date: 2025/10/13

Curator: Oladoye

Revision editor(s): Oladoye

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
Low CRC in stage I-II
Group 1 name Corresponds to the case (exposed) group for case-control studies
High CRC in stage III-IV
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The relationship between intestinal microbiome and colorectal cancer (CRC) progression
Group 0 sample size Number of subjects in the control (unexposed) group
62
Group 1 sample size Number of subjects in the case (exposed) group
130
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
one month

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
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).
raw counts
Statistical test
Chi-Square
Pearson Correlation
Spearman Correlation
T-Test
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.003
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
0.05
Matched on Factors on which subjects have been matched on in a case-control study
colorectal cancer

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/13

Curator: Oladoye

Revision editor(s): Oladoye

Source: Alpha diversity details is in figure 1

Description: The abundance and diversity of intestinal microbiome may increase taxa gradually with the occurrence and progression of CRC. increased fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified as potential microbial markers for CRC staging prediction.

Abundance in Group 1: increased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks
Alistipes
Alistipes indistinctus
Parabacteroides
Ruminococcus
Proteus

Revision editor(s): Oladoye

Signature 2

Needs review

Curated date: 2025/10/13

Curator: Oladoye

Revision editor(s): Oladoye

Source: Alpha diversity details is in figure 1

Description: The abundance and diversity of intestinal microbiome may increase taxa gradually with the occurrence and progression of CRC. increased fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified as potential microbial markers for CRC staging prediction.

Abundance in Group 1: decreased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks

Revision editor(s): Oladoye

Experiment 2


Needs review

Curated date: 2025/10/14

Curator: Oladoye

Revision editor(s): Oladoye

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low CRC in stage I-II high
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Identification of intestinal microbiome associated with CRC progression, LDA Effect Size (LEfSe) analysis on fecal microbiota of CRC patients with stage I-II and III-IV respectively.
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
22
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

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

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Linear Discriminant Analysis
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)?
Not specified
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
10
Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Needs review

Curated date: 2025/10/15

Curator: Oladoye

Revision editor(s): Oladoye

Source: Figure 2

Description: Identification of intestinal microbiome associated with CRC progression and potential biomarkers of intestinal microbiome associated with CRC progression, LDA Effect Size (LEfSe) analysis on fecal microbiota of CRC patients with stage I-II and III-IV respectively

Abundance in Group 1: increased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks
Bacteria
Butyricicoccus
Parabacteroides
Sporobacter

Revision editor(s): Oladoye

Signature 2

Needs review

Curated date: 2025/10/15

Curator: Oladoye

Revision editor(s): Oladoye

Source: Figure 2

Description: Identification of intestinal microbiome associated with CRC progression and potential biomarkers of intestinal microbiome associated with CRC progression, LDA Effect Size (LEfSe) analysis on fecal microbiota of CRC patients with stage I-II and III-IV respectively

Abundance in Group 1: decreased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks
Bacteria

Revision editor(s): Oladoye

Experiment 3


Needs review

Curated date: 2025/10/14

Curator: Oladoye

Revision editor(s): Oladoye

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low CRC in stage I-II
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Relationship between CRC progression-associated microbiota and tumor-infiltrating immune cells
Group 0 sample size Number of subjects in the control (unexposed) group
17

Lab analysis

Statistical Analysis

Statistical test
Pearson Correlation
Spearman Correlation
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified
Matched on Factors on which subjects have been matched on in a case-control study
colorectal cancer


Signature 1

Needs review

Curated date: 2025/10/14

Curator: Oladoye

Revision editor(s): Oladoye

Source: Figure 4

Description: Correlation of CRC progression-related differential intestinal flora with tumor immune infiltrating cells

Abundance in Group 1: increased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks
Alistipes
Alphaproteobacteria
Carnobacteriaceae
Dolosigranulum
Rhodospirillaceae
Rhodospirillales

Revision editor(s): Oladoye

Signature 2

Needs review

Curated date: 2025/10/14

Curator: Oladoye

Revision editor(s): Oladoye

Source: Figure 4

Description: Correlation of CRC progression-related differential intestinal flora with tumor immune infiltrating cells

Abundance in Group 1: decreased abundance in High CRC in stage III-IV

NCBI Quality ControlLinks
Actinomycetales
Butyricicoccus

Revision editor(s): Oladoye

Experiment 4


incomplete

Curated date: 2025/10/15

Curator: Oladoye

Revision editor(s): Oladoye

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Identification of intestinal microbiome associated with CRC progression, LDA Effect Size (LEfSe) analysis of fecal microbiota of CRC patients with stage I-II and III-IV respectively.
Group 0 sample size Number of subjects in the control (unexposed) group
19
Sequencing type
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Not specified

Statistical Analysis

Statistical test
LEfSe
Linear Discriminant Analysis
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
10
Matched on Factors on which subjects have been matched on in a case-control study
Not specified