The Microbiome in Lung Cancer Tissue and Recurrence-Free Survival

Abstract

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 patients with non-small cell lung cancer (NSCLC). We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free (RFS) and disease-free survival (DFS), and compared microbiome diversity and composition between paired tumor and normal samples. Results: Higher richness and diversity in normal tissue were associated with reduced RFS (richness P ¼ 0.08, Shannon index P ¼ 0.03) and DFS (richness P ¼ 0.03, Shannon index P ¼ 0.02), as was normal tissue overall microbiome composition (Bray-Curtis P ¼ 0.09 for RFS and P ¼ 0.02 for DFS). In normal tissue, greater abundance of family Koribacteraceae was associated with increased RFS and DFS, whereas greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced RFS or DFS (P < 0.05). Tumor tissue diversity and overall composition were not associated with RFS or DFS. Tumor tissue had lower richness and diversity (P 0.0001) than paired normal tissue, though overall microbiome composition did not differ between the 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 patients with lung cancer.

Microbiota Core in Central Lung Cancer with Streptococcal Enrichment as a Possible Diagnostic Marker

“…In terms of beta diversity, the tissues involved in cancer and the contralateral bronchus had almost identical compositions, as its have been previously published [6,34,35] especially Pseudomonas, has been also previously corroborated [5,6,37]. Higher concentrations of Streptococcus, Blautia, Akkermansia, and Rothia were observed in patients, but Streptococcus was consistently the major marker linked to lung cancer.…”

“…Low biodiversity is usually observed in various pathologies, including cancer, but we found significantly higher alpha-diversity values in cancer than in the control group. Other authors have published analogous [8] and opposing results [5,6,35]. Moreover advanced cancer stages [36] and reduced recurrence-free survival and disease-free survival [35] have been associated with higher values of alpha diversity.…”

“…Other authors have published analogous [8] and opposing results [5,6,35]. Moreover advanced cancer stages [36] and reduced recurrence-free survival and disease-free survival [35] have been associated with higher values of alpha diversity. Eighty-eight percent of our patients were at tumor stage III or IV, and their survival was only of 198 days in the follow up.…”

“…Significant differences in the lung ecosystem have been described based on health status or a lung cancer diagnosis in sputum [33], bronchoalveolar lavage [5], protected specimen brushing [6], cytological brushing [34], and surgical tissue [7,8,35]. The major contribution of our work is the study of the microbiome surrounding central cancer via direct sampling, but our results are not necessarily applicable to the distal airway.…”

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy

“…There are also some evidences of the potential relationship between lung microbiota composition and lung cancer prognosis. In particular, Peters et al in a pilot study, performed on paired lung tumor and distal normal samples from the same lobe/segment of 19 patients with non-small cell lung cancer (NSCLC), showed that higher diversity and alteration in lung commensal bacterial composition of the unaffected lung tissue was associated with reduced diseasefree (DFS) and recurrence-free (RFS) survival [54]. In the same work, greater abundance of Koribacteraceae was associated with increased RFS and DFS, whereas greater abundance of Bacteroidaceae, Lachnospiraceae and Ruminococcaceae was associated with reduced RFS and DFS) [54] (Table 2).…”