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Published on: October 26, 2017
Pleural fluid microbiota as a biomarker for malignancy and prognosis
Benjamin Kwok1, Benjamin G Wu1,2, Ibrahim F Kocak1
1Division of Pulmonary, Critical Care, and Sleep Medicine, New York University Grossman School of Medicine, 462 First Avenue 7N21, New York, NY, 10016, USA.
Abstract:
Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis.
Insights
The microbiome of malignant pleural effusions (MPE) differs from non-malignant effusions. Specific bacteria in MPE correlate with cancer origin and patient mortality, suggesting a role for the pleural fluid microbiome in cancer progression.
Area of Science:
- Microbiology
- Oncology
- Pulmonology
Background:
- Malignant pleural effusions (MPE) are a common complication of cancer, associated with poor prognosis.
- Current diagnostic and prognostic tools for MPE focus on cellular and cell-free components.
- The role of the pleural fluid microbiome in MPE remains largely unexplored.
Purpose of the Study:
- To investigate the unique microbial composition of MPE.
- To compare the MPE microbiome with that of benign and paramalignant pleural effusions.
- To identify microbial signatures associated with MPE diagnosis, primary cancer site, and patient mortality.
Main Methods:
- 16S rRNA gene sequencing was performed on 165 pleural fluid samples.
- Samples included benign (n=16), paramalignant (n=21), MPE-Lung (n=57), MPE-Other (n=22), and Mesothelioma (n=49) effusions.
- Comparative analysis of microbial composition across different effusion types was conducted.
Main Results:
- Significant compositional differences were observed in pleural effusions from non-malignant, paramalignant, and malignant conditions.
- MPE samples showed differential enrichment of bacterial taxa based on the primary malignancy site.
- MPE-Lung and Mesothelioma were associated with oral and gut commensal bacteria (e.g., Rickettsiella, Ruminococcus).
- Mortality in MPE-Lung was linked to enrichment of specific bacteria (e.g., Methylobacterium, Blattabacterium).
Conclusions:
- The microbiome of pleural effusions varies significantly with disease state (benign, paramalignant, malignant).
- Specific bacterial communities in MPE correlate with the primary cancer site and patient survival.
- These findings highlight the potential role of host-microbiome interactions in carcinogenesis and MPE progression.
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