A real-world evidence of sputum microbiota alterations and their association with oncogenomic changes and response to targeted therapies in patients with lung cancer.

objectiveAlterations to the respiratory microbiota may contribute to lung cancer progression. This study examined real-world data to characterize sputum microbiota alterations and to assess their association with oncogenomic changes and response to targeted therapies in patients with lung cancer.

methodA total of 724 patients with lung cancer who underwent etiological examinations of their sputum were retrospectively included. Tumor tissues of 105 patients were analyzed using commercial next-generation sequencing (NGS) panels targeting 1021 genes for the initial screening stage. Amplification-refractory mutation system-polymerase chain reaction was then used to assess the presence of EGFR mutations in 316 cases in the second stage.

resultsTP53 mutations were the most frequently observed coexisting mutations with microbial infections. In contrast, EGFR mutations were commonly found in patients without microbial infections. Tumor tissues of infected patients exhibited a significantly higher level of tumor mutation burden (TMB) and a greater frequency of copy number variations, especially on chromosome 11. Specifically, Klebsiella pneumoniae infection was more frequently associated with cases carrying TP53 mutations; while Candida albicans and Pseudomonas aeruginosa infections were observed exclusively in cases with EGFR mutations. EGFR mutations without concurrent microbial infections were associated with a better objective response rate to EGFR tyrosine kinase inhibitors and survival benefits in patients.

conclusionsWe demonstrated that opportunistic pathogens exhibited higher infection rates in patients with TP53-mutated, TMB-H, and non-EGFR-mutated tumors. Microbial infection in patients with EGFR mutations might be an influencing factor that weakens the therapeutic efficacy.