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

Study information

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

34336726

DOI Digital object identifier for electronic documents.

10.2147/JHC.S315696

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.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): WikiWorks, Claregrieve1, Mary Bearkland

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

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,Hepatocellular carcinoma

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

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

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

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks

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, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks

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
Verrucomicrobiia
Verrucomicrobiales
Verrucomicrobiota

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): WikiWorks, Claregrieve1, Mary Bearkland

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

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): WikiWorks, Claregrieve1, Mary Bearkland, Aiyshaaaa

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

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

Revision editor(s): WikiWorks, Claregrieve1, Mary Bearkland, Aiyshaaaa

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks

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, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): WikiWorks, Claregrieve1, Mary Bearkland

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

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

Not specified

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

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-23

Curated date: 2022/10/12

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks

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, WikiWorks