Comparisons of blood, upper respiratory tract and gut viromes from patients with lung cancer and healthy persons

Abstract Lung cancer is the leading cause of cancer‐related mortality globally. Although some studies have proposed a potential association between viral infections and lung cancer pathogenesis, the evidence remains inconclusive. This study characterized the virome in blood, upper respiratory tract, and gut samples from 200 lung cancer patients and 75 healthy controls, with the goal of identifying potential microbial biomarkers for lung cancer, using viral metagenomics. Significant differences in viral diversity and composition were observed between cancer and healthy groups, with lower similarities in blood, respiratory, and gut viromes. Notably, LUSC and LUAD groups showed high similarity, with LUAD exhibiting the most diverse virome. In blood, Anelloviridae dominated in cancer patients, while Retroviridae was more abundant in specific subgroups. The upper respiratory tract virome in cancer patients was enriched with Siphoviridae and Myoviridae , contrasting with Retroviridae in healthy individuals. Gut viromes were dominated by Podoviridae and Virgaviridae in cancer patients, with Virgaviridae showing higher abundance compared to healthy controls. Alpha and beta diversity analyses indicated significant differences in blood and respiratory viromes but not in gut viromes. STAMP and LEfSe analyses identified Anelloviridae and Siphoviridae as potential biomarkers for lung cancer. Additionally, 242 anelloviruses with complete ORF1 were isolated, revealing high genetic diversity. These findings highlight distinct virome profiles in lung cancer patients, offering insights into potential diagnostic and therapeutic targets.