A lung microbial signature for postoperative recurrence in stage I-II non-small cell lung cancer.
[BACKGROUND] Postoperative recurrence remains a prevalent and lethal threat to survival in early-stage non-small cell lung cancer (NSCLC), affecting approximately 20% of patients within five years.
APA
Gu C, Qi Y, et al. (2026). A lung microbial signature for postoperative recurrence in stage I-II non-small cell lung cancer.. Respiratory research, 27(1). https://doi.org/10.1186/s12931-026-03609-2
MLA
Gu C, et al.. "A lung microbial signature for postoperative recurrence in stage I-II non-small cell lung cancer.." Respiratory research, vol. 27, no. 1, 2026.
PMID
41787488
Abstract
[BACKGROUND] Postoperative recurrence remains a prevalent and lethal threat to survival in early-stage non-small cell lung cancer (NSCLC), affecting approximately 20% of patients within five years. While emerging evidence implicates the lung microbiota and microbiota-related metabolites in carcinogenesis, their prognostic value for predicting NSCLC recurrence remains underexplored.
[METHODS] Using preoperative bronchoalveolar lavage fluid from 72 patients with stage I–II NSCLC (17 recurrence and 55 non-recurrence), we performed microbial 2bRAD-M sequencing to profile bacterial, fungal, and archaeal communities, along with untargeted metabolomics. Recurrence-associated microbial signatures were identified through machine learning approaches and network analysis.
[RESULTS] Patients with recurrence exhibited significantly reduced alpha diversity, shorter recurrence-free survival but enhanced microbial interactions compared with recurrence-free controls. We identified two predictive microbial signatures (32-species and 30-genus) that significantly outperformed conventional clinical factors, achieving mean area-under-the-curve of the receiver operating characteristic curve values of 0.92 (species-level) and 0.81 (genus-level), respectively. Notably, four potential recurrence-related drivers, namely the genera , , and , along with the species , were significantly increased in recurrence patients and associated with poorer survival. An integrated metabolomic analysis revealed that two microbiota-related metabolites, indole-3-lactic acid and pyridoxal, potentially mediated elevated recurrence risk through the tryptophan and vitamin B metabolic pathways.
[CONCLUSION] These findings elucidate the prognostic role of microbiota and metabolites in the lower respiratory tract of early-stage NSCLC, and highlight their dual potential as biomarkers and intervention targets.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12931-026-03609-2.
[METHODS] Using preoperative bronchoalveolar lavage fluid from 72 patients with stage I–II NSCLC (17 recurrence and 55 non-recurrence), we performed microbial 2bRAD-M sequencing to profile bacterial, fungal, and archaeal communities, along with untargeted metabolomics. Recurrence-associated microbial signatures were identified through machine learning approaches and network analysis.
[RESULTS] Patients with recurrence exhibited significantly reduced alpha diversity, shorter recurrence-free survival but enhanced microbial interactions compared with recurrence-free controls. We identified two predictive microbial signatures (32-species and 30-genus) that significantly outperformed conventional clinical factors, achieving mean area-under-the-curve of the receiver operating characteristic curve values of 0.92 (species-level) and 0.81 (genus-level), respectively. Notably, four potential recurrence-related drivers, namely the genera , , and , along with the species , were significantly increased in recurrence patients and associated with poorer survival. An integrated metabolomic analysis revealed that two microbiota-related metabolites, indole-3-lactic acid and pyridoxal, potentially mediated elevated recurrence risk through the tryptophan and vitamin B metabolic pathways.
[CONCLUSION] These findings elucidate the prognostic role of microbiota and metabolites in the lower respiratory tract of early-stage NSCLC, and highlight their dual potential as biomarkers and intervention targets.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12931-026-03609-2.
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