Community Dynamics of Fungi During the Progression of Human Non-Small-Cell Lung Cancer

Background: Lung cancer is the most common cancer worldwide. The correlation between lung microbiota dysbiosis and lung cancer has been explored. However, the characteristics of the lung mycobiome in lung cancer patients has not been fully examined. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from 24 patients with non-small-cell lung cancer (NSCLC) and 14 non-cancerous controls with benign mass. Results: We observed greater fungal diversity and connectivity in NSCLC patients compared to non-cancer controls. Network analysis revealed that the sum of degrees in NSCLC was more numerous, suggesting the connections of fungal communities were more active. The community networks were reconstructed in 4 main ecological modules. The module and network hubs included Vanderwaltozyma polyspora, Apiotrichum porosum, Lobosporangium transversal, Capronia epimyces and Pseudomicrostroma glucosiphilum. Random forest analysis and DESeq2 were performed to screen out distinct species in two seperate groups and 3 fungi Alternaria arborescens, Eremoyces bilateralis and Malassezia restricta were identified as potential diagnosis biomarkers for NSCLC patients. In these 3 fungi, the relative abundance of Alternaria arborescens was gradually increasing as NSCLC progressed. Conclusions: Taken together, our study innovatively proposes that changes in the structure of fungal communities in lung cancer may be closely related to lung carcinogenesis as well as its progression and the distinct species listed above could be used to detect and monitor NSCLC.