背景:VRK1是丝氨酸/苏氨酸蛋白激酶的牛痘相关激酶(VRK)家族的成员,与恶性肿瘤的发生发展有关。表达模式,预测值,VRK1在各种癌症中的生物学功能在很大程度上仍然难以捉摸,需要进一步研究。
方法:公共数据库,例如TCGA,GTEx,UCEC,用于综合分析多种癌症类型中VRK1的表达。通过单变量Cox回归和Kaplan-Meier分析评估预后意义。此外,采用Spearman的相关分析来探讨VRK1表达与多种因素之间的潜在关联。包括肿瘤微环境评分,免疫细胞浸润,和免疫相关基因。此外,为了验证调查结果,用qPCR进一步证实VRK1在HCC组织和细胞系中的差异表达,蛋白质印迹,和免疫组织化学技术。
结果:在大多数癌症类型中观察到VRK1的上调,并与ACC的预后较差有关,KICH,KIRP,LGG,LIHC,LUAD,梅索,和PCPG。在各种癌症中,VRK1表达与免疫浸润细胞呈正相关,免疫检查点相关基因,TMB,和MSI。此外,VRK1的启动子甲基化状态在不同肿瘤类型中有所不同,这种变异与某些癌症患者的预后相关。在我们的实验分析中,我们观察到VRK1在HCC组织和HCC细胞中的表达显着升高。功能上,我们发现VRK1的下调对肝癌细胞有深远的影响,导致它们的扩散显著减少,迁移,和入侵能力。
结论:VRK1的表达对多种肿瘤的预后有显著影响,并与肿瘤免疫浸润密切相关。此外,在HCC的背景下,VRK1可能作为癌基因,积极促进肿瘤进展。
VRK1 is a member of the
vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which is related to the occurrence and development of malignant tumors. The expression pattern, predictive value, and biological function of VRK1 in various cancers remain largely elusive and warrant further investigation.
Public databases, such as TCGA, GTEx, and UCEC, were utilized to comprehensively analyze the expression of VRK1 across multiple cancer types. Prognostic significance was assessed through Univariate Cox regression and Kaplan-Meier analyses. Additionally, Spearman\'s correlation analysis was employed to explore the potential associations between VRK1 expression and various factors, including tumor microenvironment scores, immune cell infiltration, and immune-related genes. Moreover, to validate the findings, differential expression of VRK1 in HCC tissues and cell lines was further confirmed using qPCR, Western blot, and immunohistochemistry techniques.
The upregulation of VRK1 was observed in most cancer types, and was associated with worse prognosis in ACC, KICH, KIRP, LGG, LIHC, LUAD, MESO, and PCPG. In various cancers, VRK1 expression exhibited positive correlations with immune infiltrating cells, immune checkpoint-related genes, TMB, and MSI. Furthermore, the promoter methylation status of VRK1 varied across different tumor types, and this variation was associated with patient prognosis in certain cancers. In our experimental analyses, we observed significantly elevated expression of VRK1 in both HCC tissues and HCC cells. Functionally, we found that the downregulation of VRK1 had a profound impact on HCC cells, leading to a significant decrease in their proliferation, migration, and invasion capabilities.
The expression of VRK1 exerts a notable influence on the prognosis of several tumors and exhibits a strong correlation with tumor immune infiltration. Moreover, in the context of HCC, VRK1 may act as an oncogene, actively promoting tumor progression.