This study investigates the role of CXCL6 in head and neck squamous carcinoma (HNSC) through comprehensive expression and methylation analyses, genetic mutation analysis, and prognostic assessment. Utilizing the UALCAN dataset, CXCL6 expression analysis revealed a significant overexpression in HNSC cells compared to normal control samples, indicating its role in HNSC proliferation. Furthermore, an analysis of CXCL6 expression across different clinical parameters showed substantial up-regulation in various cancer stages, racial groups, gender, and age groups, underscoring its fundamental role in cancer progression. Validation of CXCL6 expression using the GEPIA2.0 online tool confirmed that CXCL6 was highly expressed in HNSC development compared to control samples. An analysis of CXCL6 expression across different stages of cancer revealed dysregulation in all four stages, with the highest expression in stage II and the lowest in stage III. This study also explored the promoter methylation levels of CXCL6, establishing a significant association between HNSC samples and normal controls. Examining promoter methylation across different clinical parameters revealed considerable variations, with distinct methylation patterns observed across cancer stages, racial groups, gender, and age. Overall survival (OS) and disease-free survival (DFS) analyses using the KM plotter tool demonstrated that high CXCL6 expression was associated with poorer OS compared to low expression levels. Similarly, DFS analysis showed that patients with low CXCL6 expression experienced better DFS outcomes compared to those with high CXCL6 expression. Finally, mutational analysis using cBioPortal revealed no significant mutations in HNSC samples. These findings highlight the complex involvement of CXCL6 in HNSC pathogenesis, underscoring its potential as a prognostic biomarker and therapeutic target in HNSC management.
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