Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China (mainland).
Shantou University Medical College, Shantou, Guangdong, China (mainland).
Med Sci Monit. 2020 Aug 31;26:e925289. doi: 10.12659/MSM.925289.
BACKGROUND Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). MATERIAL AND METHODS The transcriptional data and the epigenetic and genetic alterations of CDK1, CCNB1, and CCNB2, as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. RESULTS Overall, mRNA expression of CDK1, CCNB1, and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1, CCNB1, and CCNB2 were positively correlated with infiltrating levels of CD4⁺ T cells, CD8⁺ T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. CONCLUSIONS CDK1, CCNB1, and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.
细胞周期中的 G2/M 有序转换由细胞周期蛋白依赖性激酶 1/细胞周期蛋白 B（CDK1/CCNB）复合物控制。我们旨在通过多组学分析全面研究 CDK1、CCNB1 和 CCNB2 的作用及其与肝细胞癌（HCC）中免疫浸润的关系。
使用多个数据库鉴定 CDK1、CCNB1 和 CCNB2 的转录数据以及表观遗传和遗传改变，以及它们对 HCC 患者预后的影响。然后使用 TIMER 数据库探索这些基因的表达与 HCC 中免疫浸润的相关性。
总体而言，CDK1、CCNB1 和 CCNB2 的 mRNA 在包括 HCC 在内的各种肿瘤组织中表达上调。这些基因的高表达与 HCC 患者的预后较差相关。这些基因的启动子低甲基化可能导致 HCC 肿瘤组织中更高的表达水平。这些基因的遗传改变和几个甲基化-CpG 位点与生存显著相关。值得注意的是，CDK1、CCNB1 和 CCNB2 的表达水平与 HCC 中 CD4⁺ T 细胞、CD8⁺ T 细胞、中性粒细胞、巨噬细胞和树突状细胞浸润水平呈正相关。此外，还观察到这些基因的表达与 HCC 中的各种免疫标志物，如 PD-1、PDL-1 和 CTLA-4 之间存在显著相关性。
CDK1、CCNB1 和 CCNB2 是潜在的预后生物标志物，与 HCC 中的免疫细胞浸润相关。这些基因可用于预测免疫治疗的反应。将这些基因的抑制剂与免疫疗法结合使用可能会改善 HCC 患者的生存时间。
