DAND5 Expression Correlates with HPV Status in Head and Neck Squamous Cell Carcinoma: A TCGA-based Analysis

Abstract

Head and neck squamous cell carcinoma (HNSC) is a heterogeneous malignancy in which molecular biomarkers may support tumor detection and clinically relevant subgrouping, including differences by human papillomavirus (HPV) status. DAN domain BMP antagonist family member 5 (DAND5) encodes a secreted cerberus/DAN family protein reported to antagonize extracellular transforming growth factor-β (TGF-β) superfamily signaling, including bone morphogenetic protein (BMP) and NODAL-related pathways, and is best known for developmental roles such as left-right axis specification. In this study, we performed an in silico assessment of DAND5 expression in The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma cohort (TCGA-HNSC), a publicly available cancer genomics dataset, using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), open-access web-based tools for transcriptome and clinical subgroup analysis of TCGA data. GEPIA2 analysis showed higher DAND5 expression in HNSC tumors than in normal tissues and no significant association between DAND5 expression and overall survival (OS) using a median cutoff (log-rank p = 0.4; Hazard Ratio (HR) (high) = 0.89). DAND5 exhibited a statistically significant but weak positive correlation with tumor protein p53 (TP53) mRNA expression (Pearson r = 0.097; p = 0.022). UALCAN subgroup analyses demonstrated higher DAND5 expression in tumors across stages and grades compared with normal tissue, with limited differences among tumor stages, and significantly higher expression in HPV-positive tumors than HPV-negative tumors. Collectively, these findings suggest that DAND5 may serve as a tumor-associated and HPV-associated expression marker in HNSC, but not a prognostic biomarker for OS in unstratified TCGA-HNSC under the current analysis approach.