Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype

The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in t...

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Bibliographic Details
Published in:Biomedicines 2020-09, Vol.8 (9), p.349
Main Authors: Kovaleva, Olga, Podlesnaya, Polina, Rashidova, Madina, Samoilova, Daria, Petrenko, Anatoly, Zborovskaya, Irina, Mochalnikova, Valeria, Kataev, Vladimir, Khlopko, Yuri, Plotnikov, Andrey, Gratchev, Alexei
Format: Article
Language:English
Subjects:
Adenocarcinoma
Bacteria
Deoxyribonucleic acid
DNA
Foxp3 protein
Genotype & phenotype
Gram-positive bacteria
Immunohistochemistry
Inflammation
iNOS
Lung cancer
macrophage
Medical prognosis
Metastasis
microbiome
Microbiomes
Microbiota
Nitric-oxide synthase
non-small cell lung cancer
Non-small cell lung carcinoma
Phenotypes
prognosis
rRNA 16S
Small cell lung carcinoma
Squamous cell carcinoma
Stroma
Tumors
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Summary:The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines8090349