Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of Dickkopf-1 (DKK1)

Abstract

WNT signaling pathway inhibitor Dickkopf-1 (<i>DKK1</i>) is related to cancer progression; however, its diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. In this study, multiple bioinformatic analyses were conducted to evaluate therapeutic value of <i>DKK1</i> in human cancers. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project served as data resources. The Wilcoxon rank test was performed to evaluate the expression difference of <i>DKK1</i> between cancer tissues and normal tissues. A Kaplan-Meier curve and Cox regression were used for prognosis evaluation. Single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the association of DKK1 expression with the immune cell infiltration. The potential function of DKK1 was explored by STRING and clusterProfiler. We found that the expression level of <i>DKK</i>1 is significantly different in different cancer types. Importantly, we demonstrated that <i>DKK1</i> is an independent risk factor in ESCA, LUAD, MESO, and STAD. Further analysis revealed that <i>DKK1</i> had a large effect on the immune cell infiltration and markers of certain immune cells, such as Th1 and Th2 cells. PPI network analysis and further pathway enrichment analysis indicated that <i>DKK1</i> was mainly involved in the WNT signaling pathway. Our findings suggested that <i>DKK1</i> might serve as a marker of prognosis for certain cancers by affecting the WNT signaling pathway and tumor immune microenvironment.