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Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients

BACKGROUND: Many immune checkpoint inhibitors (ICIs) have been approved in China to treat non‐small cell lung cancer (NSCLC). However, in the long term, less than 20% of patients benefit from ICIs. To maximize the benefit for NSCLC patients, it is necessary to guide the choice of immunotherapy throu...

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Autores principales: Song, Peng, Yang, Dongliang, Wang, Hanping, Cui, Xiaoxia, Si, Xiaoyan, Zhang, Xiaotong, Zhang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262920/
https://www.ncbi.nlm.nih.gov/pubmed/32329229
http://dx.doi.org/10.1111/1759-7714.13442
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author Song, Peng
Yang, Dongliang
Wang, Hanping
Cui, Xiaoxia
Si, Xiaoyan
Zhang, Xiaotong
Zhang, Li
author_facet Song, Peng
Yang, Dongliang
Wang, Hanping
Cui, Xiaoxia
Si, Xiaoyan
Zhang, Xiaotong
Zhang, Li
author_sort Song, Peng
collection PubMed
description BACKGROUND: Many immune checkpoint inhibitors (ICIs) have been approved in China to treat non‐small cell lung cancer (NSCLC). However, in the long term, less than 20% of patients benefit from ICIs. To maximize the benefit for NSCLC patients, it is necessary to guide the choice of immunotherapy through biomarkers. Recent studies have shown that gut microbiota can affect tumor response to immunotherapy and might be a potential predictive biomarker. This study analyzed the relationship between intestinal flora structure and metabolomic characteristics in NSCLC and the efficacy of ICIs. METHODS: Prospective analysis of samples from 63 patients with advanced NSCLC who attended the Department of Respiratory Medicine of the Peking Union Medical College Hospital from March 2018 to June 2019, and were prescribed programmed cell death 1 (PD‐1) inhibitors, was carried out. The follow‐up deadline was 31 December 2019. Stool samples were collected from all patients before the start of immunotherapy. DNA was extracted from all samples and libraries were constructed. This was followed by sequencing using the Illumina sequencing platform, and results were studied using a biological information data analysis process. We divided the data into two groups based on progression‐free survival (PFS) ≥ six months and PFS < six months. RESULTS: The median PFS was 7.0 months, not reaching the median overall survival (OS). We obtained 373.5 G of original sequencing data. The phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria accounted for most of the bacterial communities in the stool samples studied. Compared with the PFS < six‐month group, the patients in the PFS ≥ six‐month group had significantly higher β‐diversity in the intestinal microbiome at the baseline level. There were also differences in composition between the two groups. Samples in the PFS ≥ six‐month group were rich in Parabacteroides and Methanobrevibacter, while those in the PFS < six‐month group were rich in Veillonella, Selenomonadales, and Negativicutes. The KO, COG, and CAZy databases were used to study functional group protein families, yielding 390 (KO), 264 (COG), and 859 (CAZy) functional group abundances, with significant differences between the two groups. Bacterial metabolites analysis suggested significant differences in the metabolic potential of methanol and methane between the two groups. CONCLUSIONS: We found a close correlation between intestinal microbiome β‐diversity and anti‐PD‐1 immunotherapy response in Chinese patients with advanced NSCLC. The intestinal flora composition, functional group protein family, and KEGG metabolism also differed between the two groups. Differences in pathways and flora metabolites were also noted.
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spelling pubmed-72629202020-06-03 Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients Song, Peng Yang, Dongliang Wang, Hanping Cui, Xiaoxia Si, Xiaoyan Zhang, Xiaotong Zhang, Li Thorac Cancer Original Articles BACKGROUND: Many immune checkpoint inhibitors (ICIs) have been approved in China to treat non‐small cell lung cancer (NSCLC). However, in the long term, less than 20% of patients benefit from ICIs. To maximize the benefit for NSCLC patients, it is necessary to guide the choice of immunotherapy through biomarkers. Recent studies have shown that gut microbiota can affect tumor response to immunotherapy and might be a potential predictive biomarker. This study analyzed the relationship between intestinal flora structure and metabolomic characteristics in NSCLC and the efficacy of ICIs. METHODS: Prospective analysis of samples from 63 patients with advanced NSCLC who attended the Department of Respiratory Medicine of the Peking Union Medical College Hospital from March 2018 to June 2019, and were prescribed programmed cell death 1 (PD‐1) inhibitors, was carried out. The follow‐up deadline was 31 December 2019. Stool samples were collected from all patients before the start of immunotherapy. DNA was extracted from all samples and libraries were constructed. This was followed by sequencing using the Illumina sequencing platform, and results were studied using a biological information data analysis process. We divided the data into two groups based on progression‐free survival (PFS) ≥ six months and PFS < six months. RESULTS: The median PFS was 7.0 months, not reaching the median overall survival (OS). We obtained 373.5 G of original sequencing data. The phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria accounted for most of the bacterial communities in the stool samples studied. Compared with the PFS < six‐month group, the patients in the PFS ≥ six‐month group had significantly higher β‐diversity in the intestinal microbiome at the baseline level. There were also differences in composition between the two groups. Samples in the PFS ≥ six‐month group were rich in Parabacteroides and Methanobrevibacter, while those in the PFS < six‐month group were rich in Veillonella, Selenomonadales, and Negativicutes. The KO, COG, and CAZy databases were used to study functional group protein families, yielding 390 (KO), 264 (COG), and 859 (CAZy) functional group abundances, with significant differences between the two groups. Bacterial metabolites analysis suggested significant differences in the metabolic potential of methanol and methane between the two groups. CONCLUSIONS: We found a close correlation between intestinal microbiome β‐diversity and anti‐PD‐1 immunotherapy response in Chinese patients with advanced NSCLC. The intestinal flora composition, functional group protein family, and KEGG metabolism also differed between the two groups. Differences in pathways and flora metabolites were also noted. John Wiley & Sons Australia, Ltd 2020-04-23 2020-06 /pmc/articles/PMC7262920/ /pubmed/32329229 http://dx.doi.org/10.1111/1759-7714.13442 Text en © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Song, Peng
Yang, Dongliang
Wang, Hanping
Cui, Xiaoxia
Si, Xiaoyan
Zhang, Xiaotong
Zhang, Li
Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title_full Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title_fullStr Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title_full_unstemmed Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title_short Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients
title_sort relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in chinese nsclc patients
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262920/
https://www.ncbi.nlm.nih.gov/pubmed/32329229
http://dx.doi.org/10.1111/1759-7714.13442
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