Characterizing microbial communities and their correlation with genetic mutations in early-stage lung adenocarcinoma: implications for disease progression and therapeutic targets

Background: Lung adenocarcinoma (LUAD), the most prevalent form of lung cancer. The transition from adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) to invasive adenocarcinoma (IAC) is not fully understood. Intratumoral microbiota may play a role in LUAD progression, but comprehensive stage-wise analysis is lacking.

Methods: Tumor and bronchoalveolar lavage fluid (BALF) samples from patients with AIS/MIA or IAC were collected for next-generation sequencing to characterize microbial diversity and composition. DNA extraction involved lysing samples with nuclease and protease, followed by homogenization and elution. Sequencing libraries were prepared and sequenced on the Illumina platform. Whole exome sequencing was performed to identify somatic mutations and genetic variants. Bioinformatics analysis, including taxonomic annotation with Kraken2 and de novo assembly with MEGAHIT, was conducted to process metagenomic data. Correlation analysis was performed to link microbial species with mutated genes using custom R scripts.

Results: Metagenomic analysis revealed a distinct microbial profile in IAC compared to AIS/MIA, with increased abundance of Bacteroidetes and Firmicutes in the IAC group. Bosea sp. and Microbacterium paludicola, were less abundant in IAC, suggesting a potential protective role in early-stage disease. Conversely, Mycolicibacterium species were more prevalent in IAC, indicating a possible contribution to disease progression. Genetic sequencing identified PTPRZ1 strongly correlating with microbial composition, suggesting a mechanistic link between microbiota and genetic alterations in LUAD.

Conclusion: This study characterizes microbial communities in various stages of LUAD, revealing links between microbiota and genetic mutations. The unique microbiota suggests its role in LUAD progression and as a therapeutic target.