Microbiome Landscapes in Squamous Cell Carcinoma Tissue Microenvironments: A Comparative Analysis.

Area of Science:

• Oncology
• Microbiome Research
• Cancer Biology

Background:

• Squamous cell carcinoma (SCC) is a common cancer with varied origins but shared molecular characteristics.
• The microbial landscape within the tumor microenvironment of different SCC types is not well understood.

Purpose of the Study:

• To investigate shared microbial landscapes across five distinct anatomical sites of squamous cell carcinoma.
• To identify common bacterial genera and their differential abundance in tumor versus adjacent normal tissues.

Main Methods:

• Analysis of RNA sequencing data from 419 SCC samples across cutaneous, esophageal, lung, head and neck, and cervical sites.
• Utilized MaAsLin2 for differential microbial abundance assessment between tumor and normal tissues.
• External validation cohorts (156 samples) were used to confirm key findings via AUROC analysis.

Main Results:

• Identified 28 shared bacterial genera across all five SCC cohorts, with Staphylococcus being most abundant.
• Esophageal, head and neck, and lung SCCs showed similar dysregulated microbiota, with Clostridioides significantly upregulated.
• Several bacterial genera, including Bradyrhizobium, Massilia, Providencia, and Ralstonia, exhibited differential expression across multiple SCC types and were validated.

Conclusions:

• While a common dysbiotic microbiota is absent due to anatomical variations, shared microbial patterns in adjacent tissues suggest a unified view of SCC.
• These findings may inform novel preventive and therapeutic strategies for squamous cell carcinoma.