CDK1, CCNB1, and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma

Abstract

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/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.

Identification and Validation of Key Genes in Hepatocellular Carcinoma by Bioinformatics Analysis

“…Among these, the cell cycle pathway is of great significance in the occurrence and development of cancer. Interestingly, many studies on HCC cell cycle pathways have shown that abnormal expression of cyclin-related genes is an important factor in the occurrence of liver cancer, and the silencing of the cyclin D1 gene inhibits the proliferation, cell cycle, and apoptosis of HCC cells [ 28 – 30 ]. Therefore, the present results suggested that the DEGs in the HCC-related PPIN may play an important role in the development of HCC.…”

<p>MAGOH/MAGOHB Inhibits the Tumorigenesis of Gastric Cancer via Inactivation of b-RAF/MEK/ERK Signaling</p>

“…Cyclin B1, CDK1 and p27 Kip1 were key mediators in cell cycle distribution. [22][23][24] Cyclin B1 played a key role in G2/M phase of cell cycle distribution. 25 Downregulation of CDK1 could induce G2/M arrest, 26 while p27 Kip1 was negatively correlated with cell growth.…”

miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1

“…Overexpression of CDK1 promotes the proliferation, invasion, and migration of CRC cells, indicating that CDK1 has a promoting role in the development of CRC. Some researchers have found that CDK1 and cyclin B1 may be potential diagnostic biomarkers for rhabdomyosarcoma and hepatocellular carcinoma [ 19 , 20 ]. As discovered by Yamamura et al, phosphorylated CDK1 (p-CDK1), p-CDK2, cyclin B1, and cyclin E1 levels increase within cholangiocarcinoma tissues; in addition, p-CDK1 and cyclin B1 nuclear levels positively correlate with the clinical stage and with lymph node metastasis, while the expression of p-CDK 1 is related to poor patient survival [ 21 ].…”