Distinct tumor bacterial microbiome in lung adenocarcinomas manifested as radiological subsolid nodules

Abstract

Objectives: Increasing evidence indicates that microbiota dysbiosis in the human body may play vital roles in carcinogenesis. However, the relationship between microbiome and lung cancer remains unclear. In this study, we aimed to characterize the microbiome in early stage of lung adenocarcinoma (LUAD), which presented as subsolid nodules (SSN) or solid nodules (SN). Materials and Methods: We performed 16S rRNA sequencing of 35 pairs (10 SSN and 25 SN) of LUAD tumor tissues and paired adjacent normal tissues. Machine learning was used to identify microbial signatures and construct predictive models. Results: SSN has higher microbiome richness and diversity compared with SN (richness p = 0.017, Shannon index p = 0.17), and the microbiome composition of SSN is distinct from that of SN (Bray-Curtis p = 0.013, unweighted unifrac p = 0.001). Phylum Chloroflexi (p = 0.009), Gemmatimonadetes (p = 0.018) and genus including Cloacibacterium (p = 0.003), Subdoligranulum (p = 0.002), and Mycobacterium (p = 0.034) were significantly increased in SSN. Tumor and normal tissues had similar richness and diversity, as well as overall microbiome composition. Probiotics with anti-cancer potential, like Lactobacillus, showed elevated levels in normal tissues (p = 0.018). A random forest model with 20 genera-based biomarkers achieved high accuracy for LUAD prediction (area under curve, AUC = 0.879). Meanwhile, a five genera-based signature can accurately discriminate SSN between SN (AUC = 0.950). Cross-validation of these two models also showed high predictive performance (LUAD AUC = 0.813, SSN AUC = 0.933). Conclusions: This study demonstrates, for the first time, the tumor bacterial microbiome composition of LUAD manifested as SSN is distinct from that presented as SN, which adds new knowledge to SSN in the perspective of microbiome. Furthermore, microbiome signatures showed good performance to predict LUAD or SSN.

Keywords

• Lung adenocarcinoma
• Microbiome
• Subsolid nodules
• Biomarker