Integrated analysis of microbiome and metabolome reveals signatures in PDAC tumorigenesis and prognosis
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Fang Y, Liu X, Ren J, Wang X, Zhou F, Huang S, You L, Zhao Y
Journal
Microbiology spectrum
Year
2024
Keywords:
PDAC, carcinogenesis, metabolome, microbial metabolism, microbiota, pancreatic ductal adenocarcinoma
UNLABELLED: Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of Ralstonia pickettii_B was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine. IMPORTANCE: We conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of Ralstonia pickettii_B. Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
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
- Pancreas Pancreas,pancreas
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Pancreatic ductal adenocarcinoma ductal adenocarcinoma of pancreas,ductal adenocarcinoma of the pancreas,malignant neoplasm of duct of Wirsung,pancreas ductal adenocarcinoma,pancreatic duct adenocarcinoma,pancreatic duct cancer,pancreatic ductal adenocarcinoma,pancreatic ductal carcinoma,pancreatic tubular adenocarcinoma,Pancreatic ductal adenocarcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Normal Adjacent Tissue (NAT)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Pancreatic ductal adenocarcinoma (PDAC)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Pancreatic ductal adenocarcinoma tumor samples
- Group 0 sample size Number of subjects in the control (unexposed) group
- 105
- Group 1 sample size Number of subjects in the case (exposed) group
- 103
Lab analysis
- 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
- 2b-RAD
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- MaAsLin2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.25
- 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
- body mass index, Confounders controlled for: "Metastasis" 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.Metastasis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Figure 2A,B and Table S1
Description: Differential taxa at the species and genus level identified by MaAsLin2 (*q < 0.25).
Abundance in Group 1: increased abundance in Pancreatic ductal adenocarcinoma (PDAC)
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium | ||
| Cutibacterium | ||
| Cutibacterium acnes | ||
| Cutibacterium granulosum | ||
| Staphylococcus | ||
| Staphylococcus aureus |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Figure 2A, B and Table S1
Description: Differential taxa at the species and genus level identified by MaAsLin2 (*q < 0.25).
Abundance in Group 1: decreased abundance in Pancreatic ductal adenocarcinoma (PDAC)
Revision editor(s): MyleeeA
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Pancreatic ductal adenocarcinoma tumor samples.
Lab analysis
Statistical Analysis
- 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)?
- No
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Figure 2C and D
Description: Differential taxa at the species and genus level identified by LefSe.
Abundance in Group 1: increased abundance in Pancreatic ductal adenocarcinoma (PDAC)
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus | ||
| Staphylococcus aureus |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Figure 2C and D
Description: Differential taxa at the species and genus level identified by LefSe.
Abundance in Group 1: decreased abundance in Pancreatic ductal adenocarcinoma (PDAC)
Revision editor(s): MyleeeA
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- M1 distant metastasis stage M1 distant metastasis stage,m1 distant metastasis stage
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- M1 stage (Decreased)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- M1 stage (Increased)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The tumor stage was evaluated based on the TNM staging system. M1 Stage (Metastasis stage) is the Distant Metastasis stage where cancer has spread to other part of the body.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 3
- Group 1 sample size Number of subjects in the case (exposed) group
- 3
Lab analysis
Statistical Analysis
- Statistical test
- MaAsLin2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.25
- 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
- body mass index, Confounders controlled for: "Metastasis" 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.Metastasis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Supplementary Table 1
Description: Differential taxa at the species level identified by MaAsLin2 (*q < 0.25).
Abundance in Group 1: increased abundance in M1 stage (Increased)
| NCBI | Quality Control | Links |
|---|---|---|
| Massilia timonae | ||
| Brevundimonas diminuta | ||
| Pseudomonas fulva | ||
| Dietzia maris |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Supplementary Table 1
Description: Differential taxa at the species level identified by MaAsLin2 (*q < 0.25).
Abundance in Group 1: decreased abundance in M1 stage (Increased)
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonas sp. |
Revision editor(s): MyleeeA
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Cancer or benign tumor cell proliferation disorder,neoplasm,Cancer or benign tumor,cancer or benign tumor
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Node Stage (N)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Tumor Stage (T)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The tumor stage was evaluated based on the TNM staging system.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 105
- Group 1 sample size Number of subjects in the case (exposed) group
- 105
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- 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)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Supplementary Figure 2
Description: Differential Microbial taxa between T stage and N stage identified by LefSe.
Abundance in Group 1: increased abundance in Tumor Stage (T)
| NCBI | Quality Control | Links |
|---|---|---|
| Acidovorax | ||
| Faecalibacterium | ||
| Faecalibaculum rodentium | ||
| Friedmanniella | ||
| Staphylococcaceae | ||
| Staphylococcus | ||
| Staphylococcus aureus | ||
| StaphylococcalesStaphylococcales |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Source: Supplementary Figure 2
Description: Differential Microbial taxa between T stage and N stage identified by LefSe.
Abundance in Group 1: decreased abundance in Tumor Stage (T)
Revision editor(s): MyleeeA
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