头颈部鳞癌中酪蛋白激酶1γ2的表达及临床相关性研究

Expression and clinical correlation of casein kinase 1γ2 in head and neck squamous cell carcinoma

目的探究酪蛋白激酶1γ2(CSNK1G2)在头颈部鳞癌(HNSC)发生和发展中的作用。方法采用基于癌症基因组图谱(TCGA)数据库的UALCAN和LinkedOmics数据库分析HNSC中CSNK1G2的mRNA表达量、甲基化、拷贝数突变与临床指标之间的相关性以及CSNK1G2相关共表达基因和蛋白。对肿瘤临床标本进行实时荧光定量PCR(RT-qPCR)以验证CSNK1G2在HNSC中的表达情况。利用STRING数据库对CSNK1G2表达相关蛋白进行蛋白互作网络分析。结果UALCAN分析结果显示,HNSC癌组织中的CSNK1G2 mRNA表达量高于正常组织(P<0.001);分化程度低和人乳头瘤病毒(HPV)阳性患者的HNSC癌组织中CSNK1G2 mRNA表达量均上调(均P<0.05);而不同病理分期、不同年龄阶段和不同淋巴结转移分期(N分期)患者其HNSC癌组织中的CSNK1G2 mRNA表达量差异均无统计学意义(均P>0.05)。RT-qPCR结果证实HNSC癌组织中的CSNK1G2 mRNA表达量高于癌旁组织(P<0.05)。LinkedOmincs相关性分析结果发现,CSNK1G2 mRNA表达量与CSNK1G2拷贝数突变呈正相关(P<0.001),而与其甲基化呈负相关(P<0.001)。生存分析结果发现,高CSNK1G2 mRNA表达和拷贝数突变预示着更高的生存率(P=0.033,P=0.015),而甲基化水平与生存率无关(P=0.458)。基因富集分析结果显示,CSNK1G2相关的共表达基因主要存在于DNA复制等环节。STRING蛋白互作网络分析结果显示,TP53、CHEK1、CHEK2可能是与CSNK1G2高表达明显相关的关键蛋白。结论CSNK1G2可能与TP53、CHEK1、CHEK2相关蛋白协同促进HNSC的发生和增殖,但不影响其转移和扩散。HNSC中CSNK1G2表达上调可能预示着更好的生存预后。

Objective To explore the role of casein kinase 1 gamma 2(CSNK1G2)in the development and progression of head and neck squamous cell carcinoma(HNSC).Methods Based on the Cancer Genome Atlas(TCGA),LinkedOmics and UALCAN were used to analyze the relationship among the mRNA expression of CSNK1G2,methylation,copy number variation and clinical indicators in HNSC,as well as to analysis CSNK1G2 related co-expression genes and proteins.The expression of CSNK1G2 in HNSC was verified by RT-qPCR experiments of clinical samples.Protein interaction network analysis on CSNK1G2 expression-related proteins was performed using STRING database.Results UALCAN analysis showed that the expression of CSNK1G2 mRNA in HNSC was higher than that in normal tissues(P<0.001),and the expression of CSNK1G2 mRNA was up-regulated in lower differentiation and Human Papilloma Virus(HPV)-positive HNSC(all P<0.05).But in HNSC with different pathological stages,different age stages and different lymph node metastasis stages(N stage),there was no difference in the amount of CSNK1G2 mRNA expression(all P>0.05).The RT-qPCR experiment confirmed the increased expression of CSNK1G2 mRNA in HNSC.LinkedOmincs analysis results showed that CSNK1G2 mRNA expression was positively correlated with CSNK1G2 copy number variation(P<0.001)and negatively correlated with methylation(P<0.001).Survival analysis results showed that high CSNK1G2 mRNA expression and copy number mutations predicted better survival(P=0.033,P=0.015),while methylation levels were not associated with survival(P=0.458).Gene set enrichment analysis results showed that CSNK1G2-related co-expression genes were mainly in DNA replication.The STRING's protein interaction network analysis results showed that TP53,CHEK1,and CHEK2 may be key proteins.These proteins are significantly associated with high expression levels of CSNK1G2.Conclusions CSNK1G2 may cooperate with TP53,CHEK1 and CHEK2 related proteins to promote the development of HNSC and tumor proliferation,but does not affect the metastasis and spread of HNSC.An increase in the expression of CSNK1G2 in HNSC may indicate a better survival prognosis.