| Summary: | Abstract Introduction Lung cancer is the most prevalent cancer with high mortality in China, and it is associated with the dysbiosis of the lung microbiome. This study attempted to screen for specific microorganisms as potential biomarkers for distinguishing benign lung disease from lung cancer. Methods Bronchoalveolar lavage fluid (BALF) sample was selected in the study instead of saliva to avoid contamination with oral microorganisms, and microbial taxonomic and functional differences in BALF samples from patients with lung cancer and those with those from patients with benign lung diseases were performed based on metagenomic next‐generation sequencing, for the first time, so that microorganisms other than bacteria could be included. Results The results showed that the intrasample diversity of malignant samples was different from benign samples, and the microbial differences among malignant samples were smaller, with lower microbial diversity, significantly changed microbial abundance and metabolic functions. Metabolic function analysis revealed amino acid‐related metabolism was more prevalent in benign samples, whereas carbohydrate‐related metabolism was more prevalent in malignant samples. By LEfSe, Metastat and Random Forest analysis, we identified a series of important differential microorganisms. Importantly, the model combining five key genera plus one tumor marker (neuron‐specific enolase) as indicators presented the optimal disease typing performance. Conclusion Thus results suggest the value of these differential microorganisms enriched in tumors in mechanism research and may be potential new targets for lung cancer therapy. More importantly, the biomarkers identified in this study can be conducive to improve the clinical diagnosis of lung cancer and have good application prospects.
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