Gut microbial species and metabolic pathways associated with response to treatment with immune checkpoint inhibitors in metastatic melanoma
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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
Wind TT, Gacesa R, Vich Vila A, de Haan JJ, Jalving M, Weersma RK, Hospers GAP
Journal
Melanoma research
Year
2020
In patients with metastatic cancer, gut microbiome composition differs between responder and non-responders to immune checkpoint inhibitors. However, there is little consensus on the microbiome taxa associated with response or lack of response. Additionally, recognized confounders of gut microbiome composition have generally not been taken into account. In this study, metagenomic shotgun sequencing was performed on freshly frozen pre-treatment stool samples from 25 patients (12 responders and 13 non-responders) with unresectable metastatic melanoma treated with immune checkpoint inhibitors. We observed no significant differences in alpha-diversity and bacterial prevalence between responders and non-responders (P > 0.05). In a zero-inflated multivariate analysis, correcting for important confounders such as age, BMI and use of antibiotics, 68 taxa showed differential abundance between responders and non-responders (false-discovery rate < 0.05). Cox-regression analysis showed longer overall survival for carriers of Streptococcus parasanguinis [hazard ratio (HR): 6.9] and longer progression-free survival for carriers of Bacteroides massiliensis (HR: 3.79). In contrast, carriership of Peptostreptococcaceae (unclassified species) was associated with shorter overall survival (HR 0.18) and progression-free survival (HR 0.11). Finally, 17 microbial pathways differentially abundant between responder and non-responders were observed. These results underline the association between gut microbiome composition and response to immune checkpoint inhibitor therapy in a cohort of patients with cutaneous melanoma.
Experiment 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/12
Subjects
- Location of subjects
- Netherlands
- 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
- Response to immunochemotherapy Response to immunochemotherapy,response to immunochemotherapy
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Melanoma patients with a confirmed response, defined as a complete response, partial response (PR) or stable disease (SD) according to RECIST 12 weeks after start of therapy that was ongoing at the next radiological evaluation, were labelled ‘responder’. In order to include late responders in our analysis, patients with progressive disease (PD) on the first radiological evaluation but a response at the second radiological evaluation compared to baseline were also labelled ‘responder’.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 13
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
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
- Statistical test
- Fisher's Exact Test
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, antibiotic exposure, sex, Confounders controlled for: "M-stage" 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.M-stage, Confounders controlled for: "LDH-level" 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.LDH-level, Confounders controlled for: "systemic therapy" 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.systemic therapy, Confounders controlled for: "previous anti-melanoma therapy" 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.previous anti-melanoma therapy, Confounders controlled for: "PPI use" 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.PPI use, Confounders controlled for: "colitis during ICI therapy" 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.colitis during ICI therapy
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/12
Source: Figure 3
Description: Differentially abundant taxa in responders vs non-responders (FDR cut-off = 0.05)
Abundance in Group 1: increased abundance in Responders
Revision editor(s): Sharmilac, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/12
Source: Figure 3
Description: Differentially abundant taxa in responders vs non-responders (FDR cut-off = 0.05)
Abundance in Group 1: decreased abundance in Responders
Revision editor(s): Sharmilac, Claregrieve1
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