Interaction between the microbiome and TP53 in human lung cancer

Area of Science:

• Microbiology
• Oncology
• Genomics

Background:

• Lung cancer is a leading cause of cancer death globally.
• Cigarette smoke, a primary risk factor, compromises lung epithelial barrier integrity.
• Somatic mutations and smoking may induce a dysbiotic lung microbiota linked to carcinogenesis.

Purpose of the Study:

• To investigate the association between lung microbiota, somatic mutations, and smoking in lung cancer.
• To identify specific bacterial taxa linked to lung carcinogenesis.
• To explore potential diagnostic biomarkers for lung cancer.

Main Methods:

• 16S ribosomal RNA (rRNA) bacterial gene sequencing on lung tissue from controls and cancer cases.
• Analysis of The Cancer Genome Atlas (TCGA) RNA-sequencing data for validation.
• Fluorescent in situ hybridization (FISH) to confirm bacterial presence in tumor sections.

Main Results:

• Lower alpha diversity was observed in normal lung tissue compared to tumor-adjacent or tumor tissue.
• The bacterium Acidovorax was enriched in smokers with squamous cell carcinoma.
• Acidovorax abundance was higher in squamous cell carcinoma with TP53 mutations, unlike in adenocarcinomas.

Conclusions:

• Microbiome-gene and microbiome-exposure interactions are evident in squamous cell carcinoma.
• Tumors with TP53 mutations harbor a unique bacterial consortium, especially in smoking-associated cases.
• The identified bacterial signatures may serve as novel biomarkers for early lung cancer detection.