Microbiota modulate lung squamous cell carcinoma lymph node metastasis through microbiota-geneset correlation network

Area of Science:

• Oncology
• Microbiome Research
• Genomics

Background:

• The tumor-resident microbiota in lung squamous cell carcinoma (LUSC) is linked to cancer initiation and progression.
• Gut microbiome influences immunotherapy efficacy, but its role in lymph node (LN) metastasis is unclear.
• Investigating tumor microbiota's role in LN metastasis is crucial for clinical decision-making and prognosis.

Purpose of the Study:

• To explore the potential role of tumor-resident microbiota in promoting lymph node (LN) metastasis in lung squamous cell carcinoma (LUSC).
• To characterize the molecular pathogenesis of LN metastasis by analyzing microbiota-geneset interactions.

Main Methods:

• Utilized RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA).
• Accessed microorganism quantification data from the cBioPortal database.
• Performed mutational signature analysis, transcriptome analysis, gene set enrichment analysis, immune infiltration, and microbiota-geneset network analysis.

Main Results:

• Identified distinct tumor microbiota compositions and microbial biomarkers in patients with and without LN metastases.
• Found upregulated gene sets (e.g., Myc Targets, E2F Targets, DNA Repair) in patients with LN metastases.
• Discovered strong correlations between Proteus and Bacteroides with gene sets related to tumor development and energy metabolism in LN metastatic patients.

Conclusions:

• Established associations between intratumor microbiota and host gene expression profiles.
• Highlighted the correlation network of Proteus and Bacteroides in the context of LN metastasis.
• Suggested that these microbial correlations may offer novel strategies for modulating lymph node metastasis.