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

OBJECTIVE: Alterations 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. METHOD: A 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. RESULTS: TP53 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. CONCLUSIONS: We 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.