An Exploratory Study for the Association of Gut Microbiome with Efficacy of Immune Checkpoint Inhibitor in Patients with Hepatocellular Carcinoma

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
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
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.

Experiment 1


Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

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
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
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

Statistical test
LEfSe
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

Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 3a

Description: Figure 3 Compositional differences in baseline gut microbiome. The differentially abundant taxa in the baseline gut microbiome were analyzed with linear discriminate analysis coupled with effect size measurements (LEfSe) projected with a histogram. The length indicates the effect size associated with a taxon. LDA > 3 in the baseline 16S rRNA sequencing cohort were considered statistically different.

Abundance in Group 1: increased abundance in Responders to Immune checkpoint inhibitors

NCBI Links
Succinivibrio
Tyzzerella

Revision editor(s): Mary Bearkland

Signature 2

Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 3a

Description: Figure 3 Compositional differences in baseline gut microbiome. The differentially abundant taxa in the baseline gut microbiome were analyzed with linear discriminate analysis coupled with effect size measurements (LEfSe) projected with a histogram. The length indicates the effect size associated with a taxon. LDA > 3 in the baseline 16S rRNA sequencing cohort and LDA >2 in the baseline shotgun whole-genome sequencing subset were considered statistically different. (A) R (responders; green) vs NR (nonresponders; red);

Abundance in Group 1: decreased abundance in Responders to Immune checkpoint inhibitors

NCBI Links
Peptostreptococcaceae
Verrucomicrobiota
Verrucomicrobiae
Akkermansia
Akkermansiaceae
Verrucomicrobiales

Revision editor(s): Mary Bearkland

Experiment 2


Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
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

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
LEfSe
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

Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Aiyshaaaa

Source: Figure 3a

Description: Figure 3 Compositional differences in baseline gut microbiome. The differentially abundant taxa in the baseline gut microbiome were analyzed with linear discriminate analysis coupled with effect size measurements (LEfSe) projected with a histogram. The length indicates the effect size associated with a taxon. LDA > 3 in the baseline 16S rRNA sequencing cohort were considered statistically different.

Abundance in Group 1: increased abundance in Disease control with Immune checkpoint inhibitors

NCBI Links
Acidaminococcus
Actinomycetota
Aeromonadales
Alloprevotella
Atopobiaceae
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Blautia
Blautia obeum
Coprococcus
Coriobacteriales
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Lachnospira
Megasphaera
Succinatimonas
Succinivibrionaceae
Tyzzerella
[Clostridium] scindens
Coriobacteriia

Revision editor(s): Mary Bearkland, Aiyshaaaa

Signature 2

Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 3a

Description: Figure 3 Compositional differences in baseline gut microbiome. The differentially abundant taxa in the baseline gut microbiome were analyzed with linear discriminate analysis coupled with effect size measurements (LEfSe) projected with a histogram. The length indicates the effect size associated with a taxon. LDA > 3 in the baseline 16S rRNA sequencing cohort were considered statistically different.

Abundance in Group 1: decreased abundance in Disease control with Immune checkpoint inhibitors

NCBI Links
Faecalibacterium

Revision editor(s): Mary Bearkland

Experiment 3


Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

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
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
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
LEfSe
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

Needs review

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 3a

Description: Figure 3 Compositional differences in baseline gut microbiome. The differentially abundant taxa in the baseline gut microbiome were analyzed with linear discriminate analysis coupled with effect size measurements (LEfSe) projected with a histogram. The length indicates the effect size associated with a taxon. LDA >2 in the baseline shotgun whole-genome sequencing subset were considered statistically different.

Abundance in Group 1: decreased abundance in Responders to Immune checkpoint inhibitors

NCBI Links
Alloprevotella
Alloprevotella sp.

Revision editor(s): Mary Bearkland