Abstract
Background: Head and neck squamous cell carcinoma (HNSC) is a prevalent and aggressive cancer, with ERBB2 (also known as HER2) being a gene of interest due to its role in various cancers. This study investigates the expression, promoter methylation, and potential prognostic significance of ERBB2 in HNSC, aiming to elucidate its role in the disease's progression and potential as a biomarker. Methods: This study utilized multiple bioinformatics tools and databases, including UALCAN, GEPIA2, and cBioPortal, to perform expression and methylation analyses, survival assessments, and gene enrichment studies. Validation was conducted using RT-qPCR in HNSC and normal cell lines. Results: ERBB2 expression was significantly down-regulated in HNSC samples compared to normal tissues. This down-regulation was consistent across various clinical parameters, including age, gender, race, and cancer stages. The ERBB2 promoter was significantly hypermethylated in HNSC samples compared to normal samples, providing a potential mechanism for its reduced expression. Kaplan-Meier analysis revealed that low ERBB2 expression was associated with poorer overall survival in HNSC patients. Functional enrichment analyses indicated that ERBB2 and its associated genes are involved in critical pathways such as the ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance, and the PI3K-Akt signaling pathway. Analysis of genetic mutations in ERBB2 showed a low mutation frequency (3%) in HNSC samples, suggesting a minor role of these mutations in disease progression. RT-qPCR analysis confirmed lower ERBB2 expression in HNSC cell lines (FaDu and Cal27) compared to normal control cell lines (HOK and HaCaT). Conclusion: The study highlights the significant down-regulation and promoter hypermethylation of ERBB2 in HNSC, which correlates with poorer survival outcomes. These findings suggest that ERBB2 down-regulation plays a crucial role in HNSC pathogenesis and may serve as a potential prognostic biomarker and therapeutic target in this cancer type.
Published Version
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