Abstract
This study analyzed oral squamous cell carcinoma (OSCC) genomes and transcriptomes in relation to perineural invasion (PNI) and prognosis using Cancer Genome Atlas data and validated these results with GSE41613 data. Gene set enrichment analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted. We identified 22 DNA mutations associated with both overall survival (OS) and PNI. Among them, TGFBR1 and RPS6KA4 mRNAs were overexpressed, while TYRO3 and GPR137 mRNAs were underexpressed in PNI patients. Among the 141 mRNA genes associated with both OS and PNI, we found overlap with PNI-related DNA mutations, including ZNF43, TEX10, TPSD1, and PSD3. In GSE41613 data, TGFBR1, RPS6KA4, TYRO3, GPR137, TEX10 and TPSD1 mRNAs were expressed differently according to the prognosis. The 22 DNA-mutated genes clustered into nervous system development, regulation of DNA-templated transcription, and transforming growth factor beta binding. GSEA analysis of mRNAs revealed upregulation of hallmarks epithelial mesenchymal transition (EMT), TNFα signaling via NF-κB, and IL2 STAT5 signaling. EMT upregulation aligned with the TGFBR1 DNA mutation, supporting its significance in PNI. These findings suggest a potential role of PNI genes in the prognosis of OSCC, providing insights for diagnosis and treatment of OSCC.
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