Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers

Abstract Background The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unk...

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Main Authors: Yaohui Sun, Zhiming Gan, Xiaojin Wang, Jian Liu, Wei Zhong, Zhiyan Zhang, Jiebin Zuo, Hang Zhong, Xiuting Huang, Zhixiang Yan, Qingdong Cao
Format: Article
Language:English
Published: BMC 2024-07-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-024-05485-0
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author Yaohui Sun
Zhiming Gan
Xiaojin Wang
Jian Liu
Wei Zhong
Zhiyan Zhang
Jiebin Zuo
Hang Zhong
Xiuting Huang
Zhixiang Yan
Qingdong Cao
author_facet Yaohui Sun
Zhiming Gan
Xiaojin Wang
Jian Liu
Wei Zhong
Zhiyan Zhang
Jiebin Zuo
Hang Zhong
Xiuting Huang
Zhixiang Yan
Qingdong Cao
author_sort Yaohui Sun
collection DOAJ
description Abstract Background The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. Methods A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. Results We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. Conclusions Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.
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publishDate 2024-07-01
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series Journal of Translational Medicine
spelling doaj-art-1a25d366fb5c4fae8322cac0c1df4f0c2025-08-20T03:46:12ZengBMCJournal of Translational Medicine1479-58762024-07-0122112110.1186/s12967-024-05485-0Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokersYaohui Sun0Zhiming Gan1Xiaojin Wang2Jian Liu3Wei Zhong4Zhiyan Zhang5Jiebin Zuo6Hang Zhong7Xiuting Huang8Zhixiang Yan9Qingdong Cao10Department of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityCardiovascular Disease Center, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityAbstract Background The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. Methods A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. Results We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. Conclusions Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.https://doi.org/10.1186/s12967-024-05485-0ES-LUADIntratumoral microbiomeMulti-omicsCorrelation analysisNon-invasive diagnosis
spellingShingle Yaohui Sun
Zhiming Gan
Xiaojin Wang
Jian Liu
Wei Zhong
Zhiyan Zhang
Jiebin Zuo
Hang Zhong
Xiuting Huang
Zhixiang Yan
Qingdong Cao
Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
Journal of Translational Medicine
ES-LUAD
Intratumoral microbiome
Multi-omics
Correlation analysis
Non-invasive diagnosis
title Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
title_full Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
title_fullStr Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
title_full_unstemmed Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
title_short Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers
title_sort integrative metagenomic transcriptomic and proteomic analysis reveal the microbiota host interplay in early stage lung adenocarcinoma among non smokers
topic ES-LUAD
Intratumoral microbiome
Multi-omics
Correlation analysis
Non-invasive diagnosis
url https://doi.org/10.1186/s12967-024-05485-0
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