Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common cancer associated with elevated mortality rates. Exosomes, diminutive extracellular vesicles, significantly contribute to tumour development, immunological evasion, and treatment resistance. Identifying exosome-associated biomarkers in HNSCC may improve early diagnosis, treatment targeting, and patient classification. METHODS: We acquired four publically accessible HNSCC gene expression datasets from the Gene Expression Omnibus (GEO) database and mitigated batch effects utilising the ComBat technique. Differential expression analysis and exosome-related gene screening found a collection of markedly exosome-associated differentially expressed genes (ERDEGs). Subsequently, 10 key exosome-related genes were further screened by combining three machine learning methods, LASSO regression, SVM-RFE and RF, and a clinical prediction model was constructed. Furthermore, we thoroughly investigated the biological roles of these genes in HNSCC and their prospective treatment implications via functional enrichment analysis, immune microenvironment assessment, and molecular docking confirmation. RESULTS: The study indicated that 10 pivotal exosome-related genes identified by the machine learning method had considerable differential expression in HNSCC. Clinical prediction models developed from these genes have shown high accuracy in prognostic evaluations of HNSCC patients. Analysis of the immunological microenvironment indicated varying immune cell infiltration in HNSCC, and the association with ERDEGs proposed a potential mechanism for immune evasion. Molecular docking validation indicated novel small molecule medicines targeting these genes, establishing a theoretical foundation for pharmacological therapy in HNSCC. CONCLUSION: This research identifies new exosome-related indicators for HNSCC through machine learning methodologies. The suggested biomarkers, particularly ANGPTL1, exhibit significant promise for diagnostic and prognostic uses. The investigation of the immunological microenvironment yields insights into immune modulation in HNSCC, presenting novel avenues for therapeutic targeting.