The Microbiome in Lung Cancer Tissue and Recurrence-Free Survival

Background: Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been studied. Methods: In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 non-small cell lung cancer patients. We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free and disease-free survival, and compared microbiome diversity and composition between paired tumor and normal samples. Results: Higher richness and diversity in normal tissue were associated with reduced recurrence-free survival (richness p=0.08, Shannon index p=0.03) and disease-free survival (richness p=0.03, Shannon index p=0.02), as was normal tissue overall microbiome composition (Bray-Curtis p=0.09 for recurrence-free and p=0.02 for disease-free survival). In normal tissue, greater abundance of family Koribacteraceae was associated with increased recurrence-free and disease-free survival, while greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced recurrence-free or disease-free survival (p<0.05). Tumor tissue diversity and overall composition were not associated with recurrence-free or disease-free survival. Tumor tissue had lower richness and diversity (p≤0.0001) than paired normal tissue, though overall microbiome composition did not differ between paired samples. Conclusions: We demonstrate, for the first time, a potential relationship between the normal lung microbiota and lung cancer prognosis, which requires confirmation in a larger study. Impact: Definition of bacterial biomarkers of prognosis may lead to improved survival outcomes for lung cancer patients.