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Dickkopf-1 is a Prognostic Biomarker and Correlated With Immune Infiltrates in Head and Neck Squamous Cell Carcinoma


 Background: Head and neck squamous cell carcinoma(HNSCC) has a high level of immune infiltration, and immunotherapy generates new hope to patients with head and neck tumors. It is currently one of the most promising treatments for HNSCC. Previous studies have shown that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, is related to the prognosis of a variety of tumors. DKK1 is a key mediator of immune activation and is highly associated with tumor progress and tumor microenvironment. However, the association between DKK1 expression and the prognosis of HNSCC and tumor infiltrating lymphocytes is still unknown.Objective: We aim to test the relationship between DKK1 and HNSCC prognosis and tumor infiltrating lymphocytes.Methods:We explored the DKK1 expression differences in multiple tumor tissues and normal tissues via examing TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier database to assess the correlation between DKK1 mRNA levels and clinical outcomes. Subsequently, the TIMER platform and TISIDB website were selected to evaluate the correlation between DKK1 and the level of tumor immune cell infiltration. We used cBioPortal and UCSC Xena database to further explore the reasons for the aberrant expression of DKK1 in tumorigenesis.Results: We found that DKK1 level was significantly elevated in HNSCC tissues compared with normal tissues. The expression of DKK1 is related to the tumor stage, tumor grade, histology, lymph node metastasis and worse clinical prognosis of HNSCC. In addition, DKK1 is negatively correlated with different tumor-infiltrating immune cells in HNSCC. Moreover, DKK1 is closely related to the genetic markers of a variety of immune cells. Also, the prognosis of HNSCC is worse based on the high DKK1 expression of immune cells. Copy number variation (CNV) and DNA methylation may be the cause of abnormal up-regulation of DKK1 in HNSCC.Conclusion: DKK1 can be used as a biomarker for predicting the prognosis and immune infiltration of HNSCC. These results provide us with important clues to better understand the role of DKK1 in the immunotherapy of head and neck tumors from the perspective of bioinformatics.This study provides a theoretical basis for clinical research on the treatment of head and neck squamous cell carcinoma with the DKK1 gene as a target. It may play a major role in advancing the immunotherapy of head and neck squamous cell carcinoma and enhance the therapeutic effect.