Pleural fluid microbiota as a biomarker for malignancy and prognosis

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.

Evaluating the feasibility, sensitivity, and specificity of next-generation molecular methods for pleural infection diagnosis

“…Corynebacterium and Escherichia-Shigella in SCHI0173-C and SCHI0152-C, respectively; however, these findings were not supported by the other methods. Although specimen or sampling contamination represents the most plausible explanation for these results, a recent bacterial metataxonomic study suggested that non-infective pleural disease may contain unique microbial signatures 7,35 . Strict aseptic practice during specimen collection and processing can mitigate some of these false-positive cases.…”

“…Furthermore, adeno-associated dependoparvovirus A (considered a non-pathogenic virus) and Corynebacterium was also seen in another control patient with MPE by metagenomics and bacterial metataxonomics, respectively. Although specimen or sampling contamination represents the most plausible explanation for these results, a bacterial metataxonomic study suggested that the pleural space of patients with non-infective pleural disease may not be sterile, instead potentially containing unique microbial signatures 25 . Further work in this area is needed.…”

Fatores Prognósticos no Derrame Pleural Maligno

“…Diversos biomarcadores foram utilizados como preditores prognósticos, seja através de análises séricas ou do próprio líquido pleural, com importantes resultados. Ghanim et al (2020) destacam a interação entre a expressão do marcador PD-L1 e a Proteína C-Reativa (PCR) circulante, indicando uma modulação complexa do microambiente tumoral. A significativa associação dos níveis do marcador Ki-67 com a imunoterapia sugere implicações práticas na resposta a esses agentes.…”

Liquid Biopsy in Lung Cancer: Biomarkers for the Management of Recurrence and Metastasis

“…The same study also concluded that the abundance of the lung microbiota is closely related to the development of infiltrating adenocarcinoma. Moreover, 16S rRNA gene sequencing on malignant pleural effusion (MPE) samples and controls has shown that there are compositional differences among pleural effusions related to non-malignant, para-malignant, and malignant disease [250]. The pleural fluid of MPE-Lung and Mesothelioma was associated with Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales.…”