DKK1在头颈部鳞状细胞癌中的临床价值及其调控因子分析  

DKK1 expression in head and neck squamous cell carcinoma:analysis of its clinical value and regulatory factors

作　　者：张守凯[1] 何健[1] 卫旭东[1] 梁丹茹 ZHANG Shoukai;HE Jian;WEI Xudong;LIANG Danru(Department Otolaryngology-Head Neck Surgery,Gansu Provincial People's Hospital,Lanzhou 730000,Gansu,China;Cadre Health Clinic,Gansu Provincial People's Hospital,Lanzhou 730000,Gansu,China)

机构地区：[1]甘肃省人民医院耳鼻咽喉-头颈外科,甘肃兰州730030 [2]甘肃省人民医院干部保健门诊,甘肃兰州730030

出　　处：《中国肿瘤生物治疗杂志》2020年第7期794-800,共7页Chinese Journal of Cancer Biotherapy

基　　金：甘肃省自然科学基金资助项目(No.18JR3RA051)。

摘　　要：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.

关 键 词：DICKKOPF-1 头颈部鳞状细胞癌 甲基化 预后 靶标 

分 类 号：R739.91[医药卫生—肿瘤] R730.5[医药卫生—临床医学]