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Bronchoalveolar Lavage Fluid Microbiota is Associated with the Diagnosis and Prognosis Evaluation of Lung Cancer

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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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Authors and Affiliations

Authors

Contributions

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.

Corresponding authors

Correspondence to Bi Chen or Bing Gu.

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Conflict of Interests

The authors declare no conflict of interest.

Ethical approval

The study was approved by the Medical Ethics Committee at the Affiliated Hospital of Xuzhou Medical University (XYFY2019–KL110–01).

Consent to Participate

Written informed consent was provided by all participants.

Consent for Publish

The participants consent to have their data published.

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Supplementary file1 (DOCX 344 KB)

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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 (2024). https://doi.org/10.1007/s43657-023-00135-9

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  • DOI: https://doi.org/10.1007/s43657-023-00135-9

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