Objectives: Oral squamous cell carcinoma poses a substantial global health challenge marked by rising mortality rate. Recently, immunotherapy has shown promising results in cancer management by enhancing immune response. Thus, identifying additional immune-related markers is critical for advancing immunotherapy treatments.
Methods: Data-independent acquisition (DIA) mass spectrometry approach was used to explore differentially expressed immune-related proteins in oral cancer tissues compared to adjacent non-cancerous tissues. Functional significance was identified through Gene Ontology, pathway, and network analysis. Gene expression of identified proteins was validated using transcriptomic data.
Results: DIA analysis identified 29,459 precursors corresponding to 3429 proteins. Among these, 1060 proteins were differentially expressed, with 166 being immune-related. Differentially regulated proteins were involved in innate immune response, mitochondrial ATP synthesis, and neutrophil degranulation. Pathway analysis of immune-related proteins showed perturbation in anti-tumor immunity-related pathways such as interferon signaling, TCR signaling, PD-1 signaling, and antigen processing and presentation. Significance of these pathways was further reinforced by the strong interactions identified in the protein-protein interaction network analysis. Additionally, gene expression analysis showed similar mRNA expression patterns for key proteins involved in altered pathways, including ISG15, IFIT1/3, HLA-A/C and OAS2/3.
Conclusions: Further validation of these proteins could establish them as potential targets for personalized therapy.
Keywords: Head and neck cancer; immune-related proteins; oral cancer; signalling pathways; tumour immunology.