An Exploratory Study for the Association of Gut Microbiome with Efficacy of Immune Checkpoint Inhibitor in Patients with Hepatocellular Carcinoma
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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
Shen YC, Lee PC, Kuo YL, Wu WK, Chen CC, Lei CH, Yeh CP, Hsu C, Hsu CH, Lin ZZ, Shao YY, Lu LC, Liu TH, Chen CH, Wu MS, Huang YH, Cheng AL
Journal
Journal of hepatocellular carcinoma
Year
2021
Keywords:
biomarkers, gut microbiome, hepatocellular carcinoma, immune checkpoint inhibitor
BACKGROUND: Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC). AIMS: To investigate the association between gut microbiome and efficacy of ICI in patients with HCC. METHODS: Patients with HCC who were scheduled to receive ICI were prospectively enrolled. Fecal samples were collected within 7 days before initiation of ICI (baseline) and 8 weeks later. Gut microbiome was assessed using 16S rRNA sequencing and shotgun whole-genome sequencing and correlated with objective response (complete or partial response), disease control (objective response or stable disease for ≥16 weeks), and overall survival. RESULTS: Thirty-six patients with HCC were enrolled, and 20 of them provided both baseline and 8-week feces. Alpha diversity, richness, and compositions of baseline gut microbiome indicated no difference between responders and nonresponders or between disease control and nondisease control groups. For the 20 paired feces, immunotherapy did not change any of the major microbiome features. No specific taxa were enriched in patients with objective response. Three taxa-Bifidobacterium, Coprococcus, and Acidaminococcus-were enriched in patients with disease control. However, the baseline abundance of these three taxa did not predict overall survival benefit. CONCLUSIONS: In this exploratory study, we failed to disclose any overt association of gut microbiome with the efficacy of ICI in patients with HCC. A larger prospective study is warranted for definite conclusion.
Statistical test
LEfSe
Experiment 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- 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
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- hepatocellular carcinoma adult hepatoma,adult primary hepatocellular carcinoma,cancer, hepatocellular,carcinoma of liver,carcinoma of liver cells,carcinoma of the liver cells,carcinoma, hepatocellular, malignant,HCC,hepatoblastoma,hepatoblastoma caused by somatic mutation,hepatocellular adenocarcinoma,hepatocellular cancer,hepatocellular carcinoma,hepatoma,liver and intrahepatic bile duct carcinoma,liver cancer,liver carcinoma,liver cell cancer (hepatocellular carcinoma),liver cell carcinoma,primary carcinoma of liver cells,primary carcinoma of the liver cells
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders to Immune checkpoint inhibitors
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders to Immune checkpoint inhibitors
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who responded to ICI therapy, defined as complete or partial response per Response
Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 26
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
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).
- relative abundances
- 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
- 3
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Source: Figure 3a
Description: Differential microbial abundance in baseline gut microbiome between responders and nonresponders
Abundance in Group 1: increased abundance in Responders to Immune checkpoint inhibitors
| NCBI | Quality Control | Links |
|---|---|---|
| Succinivibrio | ||
| Tyzzerella |
Revision editor(s): Mary Bearkland, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Source: Figure 3a
Description: Differential microbial abundance in baseline gut microbiome between responders and nonresponders
Abundance in Group 1: decreased abundance in Responders to Immune checkpoint inhibitors
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Akkermansiaceae | ||
| Peptostreptococcaceae | ||
| Verrucomicrobiae | ||
| Verrucomicrobiales | ||
| Verrucomicrobiota |
Revision editor(s): Mary Bearkland, Claregrieve1
Experiment 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Disease control with Immune checkpoint inhibitors
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Disease control with Immune checkpoint inhibitors
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- “disease control” was defined as objective response or stable disease lasting =16 weeks.” Objective response was defined as complete or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
- 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
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Curated date: 2022/10/12
Curator: Mary Bearkland
Revision editor(s): Mary Bearkland, Aiyshaaaa, Claregrieve1
Source: Figure 3b
Description: Differential microbial abundance in baseline gut microbiome between patients whose disease was not controlled and patients whose disease was controlled
Abundance in Group 1: increased abundance in Disease control with Immune checkpoint inhibitors
Revision editor(s): Mary Bearkland, Aiyshaaaa, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Source: Figure 3b
Description: Differential microbial abundance in baseline gut microbiome between patients whose disease was not controlled and patients whose disease was controlled
Abundance in Group 1: decreased abundance in Disease control with Immune checkpoint inhibitors
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium |
Revision editor(s): Mary Bearkland, Claregrieve1
Experiment 3
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders to Immune checkpoint inhibitors
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders to Immune checkpoint inhibitors
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- “Objective response” was defined as complete or partial response per Response
Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 12
- Group 1 sample size Number of subjects in the case (exposed) group
- 6
Lab analysis
- Sequencing type
- WMS
Statistical Analysis
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23
Source: Figure 3a
Description: Differential microbial abundance in baseline gut microbiome between responders and nonresponders
Abundance in Group 1: decreased abundance in Responders to Immune checkpoint inhibitors
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Alloprevotella sp. |
Revision editor(s): Mary Bearkland, Claregrieve1
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