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Background  Accumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor ( EGFR ) gene mutation.    Methods  The microbiota of sputum samples from 85 newly‐diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3–V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE.    Results  Alpha‐ and β‐diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera  Granulicatella  and  Actinobacillus  were significantly enriched in ES, and the genus  Actinomyces  was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with  Granulicatella . Patients with intrathoracic metastasis were associated with increased genus  Peptostreptococcus  and incomplete reductive TCA cycle, which was associated with increased  Peptostreptococcus . Genera  Parvimonas ,  Pseudomona  and L‐valine biosynthesis were positively associated with lymph node metastasis. L‐valine biosynthesis was related with increased  Pseudomona . Finally, the genus  Parvimonas  was significantly enriched in adenocarcinoma patients with  EGFR  mutation.    Conclusion  The taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and  EGFR  mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota.

The airway microbiota of non‐small cell lung cancer patients and its relationship to tumor stage and EGFR gene mutation