DOI: 10.1136/jcp-2025-210614 ISSN: 0021-9746

Targeted transcriptome profiling of oral cavity squamous cell carcinoma and histologic grade-associated gene expression patterns

Brittany Ruschkowski, Bryan Lo, Jason K Wasserman

Aims

To characterise gene expression differences between oral cavity squamous cell carcinoma (OSCC) and non-neoplastic oral mucosa using targeted transcriptome profiling and to evaluate gene expression patterns associated with tumour differentiation.

Methods

Formalin-fixed, paraffin-embedded tissue from 16 resected OSCCs (3 well differentiated, 9 moderately differentiated and 4 poorly differentiated) and 7 non-neoplastic oral mucosa samples was analysed. RNA was isolated from microdissected tissue and profiled using a targeted next-generation sequencing assay. Differential gene expression and pathway enrichment analyses were performed, including comparisons across histologic grades.

Results

OSCC demonstrated broad transcriptomic differences compared with non-neoplastic oral mucosa, with enrichment of pathways related to extracellular matrix remodelling, cell adhesion, immune regulation, oncogenic signalling and cellular metabolism. Grade-stratified analyses identified additional differences involving epithelial differentiation, immune response, lipid metabolism and oxidative phosphorylation pathways.

Conclusions

OSCC exhibits broad transcriptomic dysregulation involving extracellular matrix remodelling, cell adhesion, immune signalling, oncogenic signalling and cellular metabolism. Grade-stratified findings demonstrate molecular differences associated with tumour differentiation but require validation in larger independent cohorts. These findings may inform future studies of biomarkers and biologically relevant pathways in OSCC.

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