Abstract
The gut microbiota and cancer have been demonstrated to be closely related. However, few studies have explored the bronchoalveolar lavage fluid (BALF) microbiota in patients with lung cancer (LC), specifically the microbiota related to progression-free survival (PFS) in LC. A total of 216 BALF samples were collected including 166 LC and 50 benign pulmonary disease (N-LC) samples, and further sequenced using 16S rRNA amplicon sequencing. Enrolled LC patients were followed up, the therapeutic efficacy was assessed, and PFS was calculated. The associated clinical and microbiota sequencing data were deeply analysed. Distinct differences in the microbial profiles were evident in the lower airways of patients with LC and N-LC, which was also found between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A combined random forest model was built to distinguish NSCLC from SCLC and reached area under curves (AUCs) of 0.919 (95% CI 86.69–97.1%) and 0.893 (95% CI 79.39–99.29%) in the training and test groups, respectively. The lower alpha diversity of the BALF microbiota in NSCLC patients was significantly associated with reduced PFS, although this link was not observed in SCLC. Specifically, NSCLC with a higher abundance of f_Lachnospiraceae, s_Prevotella nigrescens and f_[Mogibacteriaceae] achieved longer PFS. The enrichment of o_Streptophyta and g_Prevotella was observed in SCLC with worse PFS. This study provided a detailed description of the characteristics of BALF microbiota in patients with NSCLC and SCLC simultaneously and provided insights into the role of the diagnosis and prognosis evaluation.
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Data Availability Statement
Sequence reads for the 216 samples have been deposited in the European Nucleotide Archive under the study number PRJEB61420.
Abbreviations
- ASVs:
-
Amplicon sequence variants
- AUC:
-
Area under the curve
- BALF:
-
Bronchoalveolar lavage fluid
- CI:
-
Confidence interval
- Faith PD:
-
Faith phylogenetic diversity
- IARC:
-
International Agency for Research on Cancer
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- LC:
-
Lung cancer
- LDA:
-
Linear discriminant analysis
- LEfSe:
-
LDA effect size
- N-LC:
-
Benign pulmonary diseases
- NSCLC:
-
Non-small cell lung cancer
- PCoA:
-
Principal coordinate analysis
- PD:
-
Progressive disease
- PERMANOVA:
-
Permutation analysis of variance
- PFS:
-
Progression-free survival
- PICRUSt:
-
Phylogenetic Investigation of Communities by Reconstruction of Unobserved States
- PR:
-
Partial response
- RECIST:
-
Response Evaluation Criteria in Solid Tumours
- ROC:
-
Receiver operating characteristic curve
- SCLC:
-
Small cell lung cancer
- SD:
-
Stable disease
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Acknowledgements
This research was supported by the National Natural Science Foundation of China (81871734, 82072380), Key R & D Program of Jiangsu Province (BE2020646), Research foundation for advanced talents of Guangdong Provincial People's Hospital (KJ012021097), and Jiangsu Province Capability Improvement Project through Science, Technology and Education (ZDXK202239).
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Conceptualization: CC, BC, BG; Methodology: ZW, XX; Formal analysis and investigation: CD, PL, YL, YY, XY; Writing—original draft preparation: CC; Writing—review and editing: CC, ZW, BC, BG; Funding acquisition: BG; Resources: BC, BG; Supervision: ZW, BC. All authors read and approved the final manuscript.
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Cheng, C., Wang, Z., Ding, C. et al. Bronchoalveolar Lavage Fluid Microbiota is Associated with the Diagnosis and Prognosis Evaluation of Lung Cancer. Phenomics 4, 125–137 (2024). https://doi.org/10.1007/s43657-023-00135-9
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DOI: https://doi.org/10.1007/s43657-023-00135-9