目的：探讨Dickkopf-1（DKK1）在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）组织中的表达及其调控机制。方法：基于TCGA数据库分析DKK1 在HNSCC组织中的表达水平及其甲基化位点与预后的关系。用GO和KEGG基因富集法分析DKK1 富集基因的信号通路。用STRING 分析DKK1 蛋白与其他蛋白质之间的相互作用。利用TargetScan 分析调控DKK1 表达的miRNA，并通过TRRUST网站分析DKK1 的转录因子。结果：DKK1 基因在HNSCC组织中高表达（P<0.01），其表达水平与患者HPV状态、年龄、病理分级、临床分期显著相关（均P<0.05）；DKK1 高表达HNSCC患者的预后较低表达者差（P<0.01）。DKK1 存在19 个甲基化位点，其中12 个在癌组织与正常组织间表达差异有统计学意义（P<0.05），11 个与HNSCC的预后显著关联（P<0.05）。此外，miRNA、circRNA、lincRNA、转录因子等也参与DKK1 的调控，共获取5 个DKK1 相关的PPI 网络可能参与HNSCC的发生、发展、侵袭和转移。结论：DKK1 在HNSCC组织中高表达，并且是HNSCC患者预后差的危险因素，DKK1在HNSCC发病过程中起重要作用，有望成为HNSCC治疗的潜在靶标。

Objective: To explore the expression and regulation mechanism of Dickkopf-1 (DKK1) in head and neck squamous cell carcinoma (HNSCC) tissues. Methods: Based on the TCGA database, the relationship of DKK1 expression in HNSCC tissues and its methylation site with patients’prognosis was analyzed. GO and KEGG gene enrichment method were used to analyze the signaling pathways of DKK1 enrichment. STRING was used to analyze the interaction between DKK1 protein and other proteins. TargetScan was used to analyze the miRNAs that regulate the expression of DKK1, and the transcription factors of DKK1 were analyzed with the TRRUST website. Results: DKK1 gene was highly expressed in HNSCC tissues (P<0.01), and its expression level was significantly correlated with the HPV status, age, pathological grade, and clinical stage of patients (all P<0.05); the prognosis of HNSCC patients with high DKK1 expression was poorer than those with low DKK1 expression (P<0.01). There were 19 methylation sites in DKK1, 12 of which were significantly different between cancer tissues and normal tissues (P<0.05), and 11 sites were significantly related to the prognosis of HNSCC (P<0.05). In addition, miRNA, circRNA, lincRNA and transcription factors, etc. also participated in the regulation of DKK1. A total of 5 DKK1-related PPI networks that may involve in the occurrence, development, invasion and metastasis of HNSCC were obtained. Conclusion: DKK1 is highly expressed in HNSCC tissues and is a risk factor for poor prognosis of HNSCC patients. DKK1 plays an important role in the pathogenesis of HNSCC and is expected to become a potential target for HNSCC treatment.

甘肃省自然科学基金资助项目（No. 18JR3RA051）