Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study
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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.
Authors
Jeong S, Liao YT, Tsai MH, Wang YK, Wu IC, Liu CJ, Wu MS, Chan TS, Chen MY, Hu PJ, Kao WY, Liu HC, Tsai MJ, Liu CY, Chang CC, Wu DC, Hsu YH
Journal
BMC microbiology
Year
2024
Keywords:
Bacteroides_caccae, Bifidobacterium_longum, Fusobacteria, GLCMANNANAUT-PWY, Lachnospiraceae_bacterium_5_1_63FAA, Streptococcus_anginosus
BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
Experiment 1
Needs review
Subjects
- Location of subjects
- Taiwan
- 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
- Gastric cancer Ca body - stomach,ca greater curvature of stomach,Ca lesser curvature - stomach,cancer of stomach,gastric cancer,gastric cancer, intestinal,gastric neoplasm,malignant gastric neoplasm,malignant gastric tumor,malignant neoplasm of body of stomach,malignant neoplasm of lesser curve of stomach,malignant neoplasm of stomach,malignant neoplasm of the stomach,malignant stomach neoplasm,malignant tumor of body of stomach,malignant tumor of greater curve of stomach,malignant tumor of lesser curve of stomach,malignant tumor of stomach,malignant tumor of the stomach,stomach cancer,Gastric cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Chronic gastritis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Gastric Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early and late stage gastric cancer.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 32
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 6 months
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
- 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)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 4.27
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Figure 2(a)
Description: Comparative analysis of differential abundance between chronic gastritis and gastric cancer at the genus levels using LEfSe.
Abundance in Group 1: increased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Coprococcus | ||
| Fusobacterium | ||
| Haemophilus | ||
| Oscillibacter | ||
| Parabacteroides | ||
| Phascolarctobacterium | ||
| Sutterella | ||
| Veillonella | ||
| unclassified Sutterellaceae |
Revision editor(s): Shulamite, Aleru Divine
Signature 2
Needs review
Source: Figure 2(a)
Description: Comparative analysis of differential abundance between chronic gastritis and gastric cancer at the genus levels using LEfSe.
Abundance in Group 1: decreased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium | ||
| Collinsella | ||
| Pseudomonas | ||
| Enterococcus | ||
| Adlercreutzia | ||
| Acinetobacter |
Revision editor(s): Shulamite, Aleru Divine
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (NIM, IM and late-stage gastric cancer))
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Early-stage gastric cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early-stage gastric cancer (Phase I and II).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 52
- Group 1 sample size Number of subjects in the case (exposed) group
- 13
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Figure 2(b)
Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using LEfSe.
Abundance in Group 1: increased abundance in Early-stage gastric cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Odoribacter | ||
| Phascolarctobacterium | ||
| Veillonella | ||
| unclassified Sutterellaceae |
Revision editor(s): Aleru Divine
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (NIM, IM and early-stage gastric cancer)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Late-stage gastric cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with late-stage gastric cancer (Phase III and IV).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 46
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Figure 2(b)
Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using LEfSe.
Abundance in Group 1: increased abundance in Late-stage gastric cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacterium | ||
| Oscillibacter | ||
| Parabacteroides | ||
| Sutterella |
Revision editor(s): Aleru Divine
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (NIM, early-stage gastric cancer and late-stage gastric cancer))
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Intestinal metaplasia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with chronic gastritis with pre-cancer lesions (intestinal metaplasia, IM)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 50
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Figure 2(b)
Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using LEfSe.
Abundance in Group 1: increased abundance in Intestinal metaplasia
| NCBI | Quality Control | Links |
|---|---|---|
| Adlercreutzia | ||
| Anaerostipes |
Revision editor(s): Aleru Divine
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (IM, early-stage gastric cancer and late-stage gastric cancer))
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-intestinal metaplasia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with chronic gastritis without pre-cancer lesions (non-intestinal metaplasia, IM)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 47
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Figure 2(b)
Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using LEfSe.
Abundance in Group 1: increased abundance in Non-intestinal metaplasia
| NCBI | Quality Control | Links |
|---|---|---|
| Acinetobacter |
Revision editor(s): Aleru Divine
Experiment 6
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Chronic gastritis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Gastric Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early and late stage gastric cancer.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 32
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Table 1
Description: Differential abundance by Wilcoxon Rank-Sum Test between chronic gastritis and gastric cancer in Phylum
Abundance in Group 1: increased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacteriota |
Revision editor(s): Aleru Divine
Signature 2
Needs review
Source: Table 1
Description: Differential abundance by Wilcoxon Rank-Sum Test between chronic gastritis and gastric cancer in Phylum
Abundance in Group 1: decreased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota |
Revision editor(s): Aleru Divine
Experiment 7
Needs review
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Statistical test
- edgeR
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Table 2
Description: Significant genera by EdgeR analysis
Abundance in Group 1: increased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus |
Revision editor(s): Aleru Divine
Signature 2
Needs review
Source: Table 2
Description: Significant genera by EdgeR analysis
Abundance in Group 1: decreased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacterium | ||
| Collinsella | ||
| Pseudomonas | ||
| Morganella |
Revision editor(s): Aleru Divine
Experiment 8
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (NIM, early-stage gastric cancer and late-stage gastric cancer))
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Intestinal metaplasia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with chronic gastritis with pre-cancer lesions (intestinal metaplasia, IM)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 50
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Table 2, text
Description: Significant genera by EdgeR analysis
Abundance in Group 1: increased abundance in Intestinal metaplasia
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacterium | ||
| Agathobacter rectalis |
Revision editor(s): Aleru Divine
Experiment 9
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Other sub-groups (IM, early-stage gastric cancer and late-stage gastric cancer))
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-intestinal metaplasia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with chronic gastritis without pre-cancer lesions (non-intestinal metaplasia, IM)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 47
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Table 2
Description: Significant genera by EdgeR analysis
Abundance in Group 1: increased abundance in Non-intestinal metaplasia
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas | ||
| Pseudomonas |
Revision editor(s): Aleru Divine
Experiment 10
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Chronic gastritis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Gastric Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early and late stage gastric cancer.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 32
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- arcsine square-root
- Statistical test
- MaAsLin2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Table 3
Description: Microbiome signatures associated with chronic gastritis and gastric cancer from MaAsLin results.
Abundance in Group 1: increased abundance in Gastric Cancer
Revision editor(s): Aleru Divine
Signature 2
Needs review
Source: Table 3
Description: Microbiome signatures associated with chronic gastritis and gastric cancer from MaAsLin results.
Abundance in Group 1: decreased abundance in Gastric Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium longum | ||
| Enterococcus faecium | ||
| Lachnospiraceae bacterium 5_1_63FAA |
Revision editor(s): Aleru Divine
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