Integrative Metatranscriptomic Analysis Reveals Disease-specific Microbiome-host Interactions in Oral Squamous Cell...

Area of Science:

• Microbiology
• Oncology
• Genomics

Background:

• Oral squamous cell carcinoma (OSCC) research has primarily used 16S rRNA sequencing for microbiome analysis.
• The functional role and host interactions of the OSCC microbiome remain largely unexplored.

Purpose of the Study:

• To simultaneously characterize the microbiome and host transcriptomes in OSCC tissues.
• To predict microbiome-host interactions in oral carcinogenesis.
• To identify key microbial players and their functional contributions to OSCC.

Main Methods:

• Laser microdissection coupled with deep metatranscriptome sequencing of tumor/adjacent normal tissues and healthy controls.
• Bioinformatic analysis integrating microbial and host transcriptomic data.
• Preliminary in vitro validation using oral cancer cell lines.

Main Results:

• Identified a transcriptionally active, multi-kingdom microbiome in OSCC tissues, distinct from healthy controls.
• Enrichment of specific taxa (e.g., Cutibacterium acnes, Malassezia restricta, HHV-6B) and bacteriophages in OSCC.
• OSCC-associated microbes correlated with upregulated host proliferation pathways, including MYC expression.
• Evidence of field cancerization in adjacent normal tissues.

Conclusions:

• The oral microbiome plays a functional role in oral carcinogenesis.
• Cutibacterium acnes may contribute to OSCC development through mechanisms like hyaluronate lyase overexpression and MYC pathway activation.
• This study offers new insights into microbiome-host interactions in OSCC, warranting further experimental validation.