Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers

Abstract Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC pat...

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Main Authors: Huijuan Chen, XueNa Yao, Chunyan Yang, Yiran Zhang, Henan Dong, Jincheng Zhai, Dongjie Fan, Qiming Zhou
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06209-8
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author Huijuan Chen
XueNa Yao
Chunyan Yang
Yiran Zhang
Henan Dong
Jincheng Zhai
Dongjie Fan
Qiming Zhou
author_facet Huijuan Chen
XueNa Yao
Chunyan Yang
Yiran Zhang
Henan Dong
Jincheng Zhai
Dongjie Fan
Qiming Zhou
author_sort Huijuan Chen
collection DOAJ
description Abstract Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC patients remained unexplored. In this study, plasma samples from 76 LC patients, 9 liver cancer patients, 11 pancreatic cancer patients, and 53 healthy controls (HCs) were collected and underwent metagenomic analyses by whole genome sequencing. The composition and relative abundance of the microbial profiles were significantly different between the LC patients and HCs. A distinct plasma-based microbial profile was observed in LC patients. By differential analysis using MaAslin, 40 significant species between LC patients and HCs were identified. Five species were selected as optimal circulating microbial biomarkers for LC. The constructed classifier based on these five species showed an AUC of 0.9592, 0.9131, and 0.8077 in the discovery, validation, and additional validation cohorts, respectively. Furthermore, metagenomic profiles of 25 lung tumor tissue and plasma paired samples were analyzed and compared. The microbial diversity was significantly increased in plasma compared with the tumor tissue. Among the 13 shared core microbial species, 10 had no difference between the tumor tissue and paired plasma. In conclusion, circulating microbial nucleic acids in the plasma have potential as biomarkers for LC liquid biopsies. The microbiome in the tumor tissue was one of the possible sources of circulating microbial nucleic acids.
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spelling doaj-art-02b44ef6f20340e4bcecbb2911db89e52025-08-20T03:00:58ZengBMCJournal of Translational Medicine1479-58762025-02-0123111310.1186/s12967-025-06209-8Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkersHuijuan Chen0XueNa Yao1Chunyan Yang2Yiran Zhang3Henan Dong4Jincheng Zhai5Dongjie Fan6Qiming Zhou7Beijing CapitalBio Medlab Co. LtdBeijing CapitalBio Medlab Co. LtdBeijing SeqTide Gene Technology Co. LtdBeijing SeqTide Gene Technology Co. LtdBeijing Best HealthCare Medical Technology Co. LtdBeijing Best HealthCare Medical Technology Co. LtdNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionSchool of Life Science and Technology, Harbin Institute of TechnologyAbstract Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC patients remained unexplored. In this study, plasma samples from 76 LC patients, 9 liver cancer patients, 11 pancreatic cancer patients, and 53 healthy controls (HCs) were collected and underwent metagenomic analyses by whole genome sequencing. The composition and relative abundance of the microbial profiles were significantly different between the LC patients and HCs. A distinct plasma-based microbial profile was observed in LC patients. By differential analysis using MaAslin, 40 significant species between LC patients and HCs were identified. Five species were selected as optimal circulating microbial biomarkers for LC. The constructed classifier based on these five species showed an AUC of 0.9592, 0.9131, and 0.8077 in the discovery, validation, and additional validation cohorts, respectively. Furthermore, metagenomic profiles of 25 lung tumor tissue and plasma paired samples were analyzed and compared. The microbial diversity was significantly increased in plasma compared with the tumor tissue. Among the 13 shared core microbial species, 10 had no difference between the tumor tissue and paired plasma. In conclusion, circulating microbial nucleic acids in the plasma have potential as biomarkers for LC liquid biopsies. The microbiome in the tumor tissue was one of the possible sources of circulating microbial nucleic acids.https://doi.org/10.1186/s12967-025-06209-8Lung cancerPlasmaWhole genome sequencingCirculating microbial nucleic acidsBiomarkers
spellingShingle Huijuan Chen
XueNa Yao
Chunyan Yang
Yiran Zhang
Henan Dong
Jincheng Zhai
Dongjie Fan
Qiming Zhou
Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
Journal of Translational Medicine
Lung cancer
Plasma
Whole genome sequencing
Circulating microbial nucleic acids
Biomarkers
title Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
title_full Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
title_fullStr Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
title_full_unstemmed Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
title_short Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
title_sort distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers
topic Lung cancer
Plasma
Whole genome sequencing
Circulating microbial nucleic acids
Biomarkers
url https://doi.org/10.1186/s12967-025-06209-8
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