Pleural fluid microbiota as a biomarker for malignancy and prognosis

Our plain-English summary of Pleural fluid microbiota as a biomarker for malignancy and prognosis, by B. Kwok, B.G. Wu, I.F. Kocak, et al (Scientific Reports, 2023).

The study

• Authors: B. Kwok, B.G. Wu, I.F. Kocak, I. Sulaiman, R. Schluger, Y. Li, R. Anwer, C. Goparaju, D.J. Ryan, M. Sagatelian, M.S. Dreier, V. Murthy, S. Rafeq, G.C. Michaud, D.H. Sterman, J.L. Bessich, H.I. Pass, L.N. Segal, J.J. Tsay
• Journal: Scientific Reports
• Published: 2023;13(1):2229
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

In plain English

This study at NYU Langone Medical Center examined bacterial DNA in pleural fluid, which collects around the lungs. The fluid came from 165 adults recruited between February 1999 and January 2021. Their effusions were benign (16), paramalignant (21), from non-small cell lung cancer (57), from other cancers (22), or from malignant pleural mesothelioma (49). Table 1 lists 31 of the 49 mesothelioma patients with a history of asbestos exposure, printed as 74% without a stated denominator. Exposure was not tested as an explanation for the findings. Using 16S rRNA gene sequencing, the authors found that bacterial composition differed among the five groups. Bacterial load was greater in the mesothelioma group, whose fluid was enriched with Legionella, Rickettsiella and Ruminococcus. Median survival was 19.6 months in the mesothelioma group. In that group, survival past the median was associated with Deinococcus, and earlier death with Prevotella. Prediction models for mesothelioma survival had area-under-the-curve values from 0.5 to 0.81. The authors stated that, without a validation set, they could not conclude they had developed a clinically useful biomarker. They also noted the study was single-center and that sequencing cannot show whether the bacteria were alive.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center study of pleural fluid samples from prospectively recruited patients, which the authors describe as cross-sectional, using 16S rRNA gene sequencing
• Who was studied: 165 adults (165 pleural fluid samples) undergoing clinically indicated pleural fluid procedures at NYU Langone Medical Center, recruited February 1999 to January 2021. Groups: Benign (n = 16), Paramalignant (n = 21), MPE-Lung (non-small cell lung cancer, n = 57), MPE-Other (n = 22), and Mesothelioma (malignant pleural mesothelioma, n = 49). Patients with an infected pleural space or small cell lung cancer were excluded.
• Exposure: The factor studied was the bacterial content (microbiota) of pleural fluid. History of asbestos exposure was recorded as a patient characteristic and compared across groups in Table 1, with p less than 0.001. The table lists these counts and percentages:
• Total: 33 (22%)
• Benign: 0 (0%)
• Paramalignant: 1 (5.0%)
• MPE-Lung: 1 (2.0%)
• MPE-Other: 0 (0%)
• Mesothelioma: 31 (74%), in a group of 49
  The article does not state the denominators behind these percentages. Exposure was not analyzed as an explanation for the microbial or survival findings. No fiber types were reported.
• Main results:
  • Bacterial composition (beta diversity) differed among the five pleural fluid groups (p less than 0.05).
  • Bacterial load was greater in the Mesothelioma group than in the other groups.
  • Pleural fluid from the Mesothelioma group was enriched with Legionella, Rickettsiella and Ruminococcus. Fluid from the MPE-Lung group was enriched with Enterococcus, Lactobacillales, Psychrobacter and Caulobacteraceae.
  • Median survival was 33.6 months in the MPE-Lung group, 36 months in the MPE-Other group and 19.6 months in the Mesothelioma group.
  • In the Mesothelioma group, survival beyond the median was associated with enrichment of Deinococcus, and early mortality with enrichment of Prevotella.
  • In the MPE-Lung group, survival beyond the median was associated with enrichment of Methylobacterium, Blattabacterium and Deinococcus, and early mortality with enrichment of Cellvibrio.
  • Bacterial concentration and overall microbiome measures did not differ significantly between patients labeled alive and those labeled deceased.
  • Random forest models predicting mortality had area under the curve values of 0.59 to 0.66 for MPE-Lung, 0.66 to 0.94 for MPE-Other, and 0.5 to 0.81 for Mesothelioma.
• The authors' conclusion: The authors concluded that they had described microbial genomic signatures in pleural fluid of patients with malignancy that were associated with distinct diagnosis and prognosis. They also stated that, lacking a validation set, they could not conclude they had developed a clinically useful biomarker.
• Limitations the authors state:
  • The study was carried out at a single center.
  • Because of the cross-sectional design, many patients had no repeat samples, so changes over time could not be analyzed.
  • 16S rRNA gene sequencing cannot show whether the bacteria detected were alive or dead; the signals may represent bacterial DNA that moved into the pleural space.
  • The prediction models were not tested in a validation cohort.
  • No tissue from the primary cancer was collected to compare with the pleural fluid.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Pleural Effusion, Mesothelioma, Carcinogenesis.

Related studies

• Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications — A. Fiorelli, G. Vicidomini, et al. (2011)
• Intratumor microbiota as a novel potential prognostic indicator in mesothelioma — F. Pentimalli, M. Krstic-Demonacos, et al. (2023)
• Biomarkers in the diagnosis of pleural diseases: a 2018 update — J.M. Porcel (2018)
• Profile of soluble factors in pleural effusions predict prognosis in mesothelioma — I.M. Dick, Y.C.G. Lee, et al. (2022)
• Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma — K. Adamic, M.M. Malovrh, et al. (2025)
• Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas — K.B. Sriram, V. Relan, et al. (2012)

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