DKK3 expression is correlated with poorer prognosis in head and neck squamous cell carcinoma: A bioinformatics study based on the TCGA database

Objective: We previously reported that dickkopf WNT signaling pathway inhibitor 3 (DKK3) expression is correlated with poorer prognosis in head and neck squamous cell carcinoma (HNSCC). Here we investigated DKK3 expression by using The Cancer Genome Atlas (TCGA) public database and bioinformatic analyses.

Methods: We used the RNA sequence data and divided the tumor samples into "DKK3-high" and "DKK3-low" groups according to median DKK3 expression. The correlations between DKK3 expression and the clinical data were investigated. Differentially expressed genes (DEGs) were detected using DESEq2 and analyzed by ShinyGO 0.77. A gene set enrichment analysis (GSEA) was also performed using GSEA software. The DEGs were also analyzed with TargetMine to establish the protein-protein interaction (PPI) network.

Results: DKK3 expression was significantly increased in cancer samples, and a high DKK3 expression was significantly associated with shorter overall survival. We identified 854 DEGs, including 284 up-regulated and 570 down-regulated. Functional enrichment analyses revealed several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with extracellular matrix remodeling. The PPI network identified COL8A1, AGTR1, FN1, P4HA3, PDGFRB, and CEP126 as the key genes.

Conclusions: These results suggested the cancer-promoting ability of DKK3, the expression of which is a promising prognostic marker and therapeutic target for HNSCC.