Elevated Expression is an Independent Unfavorable Prognostic Indicator of Survival in Head and Neck Squamous Cell Carcinoma

Purpose: DKK1 is an antagonist of the Wnt signaling pathway that has various roles in human physiology. Notably, aberrant expression is observed in several cancers. In this retrospective study, we assessed the association between expression levels and head and neck squamous cell carcinoma (HNSCC) and its prognostic value.

Materials And Methods: Using RNA-seq data from HNSCC tumors (N=520) and adjacent normal tissue (N=44) in The Cancer Genome Atlas, we evaluated expression levels. Additionally, we evaluated the association of expression levels and pathophysiological features of patients with HNSCC and the value of expression for prediction of overall survival (OS). We also explored the correlation between expression and methylation of its promoter in HNSCC.

Results: expression was significantly upregulated in HNSCC compared with normal tissues. Moreover, expression was significantly associated with smoking, alcohol abuse, sex, human papillomavirus status, tumor site, tumor invasion, and pathologic stage in HNSCC patients. Kaplan-Meier curves showed that high expression was correlated with inferior OS. In addition, univariate and multivariate analyses showed that elevated expression was an independent prognostic factor for poor OS (HR: 1.85, 95% CI: 1.31-2.62, <0.001). Regression analysis identified a strong negative correlation between expression and methylation of its promoter.

Conclusion: These findings support the hypothesis that elevated expression is modulated via methylation of its promoter and indicate that expression is a highly informative prognostic biomarker for patients with HNSCC.