Bioinformatics Analysis Of CDK1 In Hepatocellular Carcinoma

Background and Objective:Hepatocellular carcinoma(HCC)is one of the common malignancies worldwide and the leading cause of cancer-related mortality.Its pathogenic factors are mainly associated with hepatitis virus infection,excessive alcohol consumption and aflatoxin poisoning.In the past decades,the treatment of HCC mainly includes surgical resection,transplantation,ablation and chemoembolization.However,due to its strong concealment,high recurrence rate and easy metastasis,it still faces multiple challenges in treatment.Therefore,in order to improve the survival and prognosis of this malignant tumor,some scholars have proposed to screen out the markers related to the occurrence and development of HCC as the target of targeted therapy,which has become a feasible scheme for the treatment of HCC.This article will explore the expression of CDK1 in HCC and its correlation with prognosis through data mining,and conduct enrichment and immune correlation analysis,in order to provide new therapeutic targets for the treatment of HCC.Methods :1.First,the expression of CDK1 in pan-cancer was analyzed using the TIMER 2.0 database(http://timer.cistrome.org/)and GEPIA2 database(http://GEPIA2(cancer-pku.cn/)).Then downloaded HCC data from TCGAdataba se(https://portal.gdc.cancer.gov/)and GEO database(https://www.ncbi.nlm.ni h.gov/gds),and used R 4.2 software(limma package)for differential expressi-on analysis.2.The Kaplan-Meier Plotter database(liver cancer section in http://kmplot.com/analysis/)was selected for overall survival(OS)and progression-free survival(PFS)analysis.The clinical data in the TCGA database were downloaded,and the OS and PFS were also analyzed using the survival package,and the accuracy of using CDK1 to predict the 1-year,3-year,and 5-year survival of patients was evaluated.Finally,we used the Complex Heatmap package to explore the relationship between CDK1 and clinical features such as age,gender,tumor grade and stage.3.The hepatocellular carcinoma gene expression files were sorted out,and CDK1-related genes were analyzed using R software.Then,the differentially expressed genes in the high and low expression groups of CDK1 were screened,and the cluster Profiler software package was used for GO and KEGG enrichment analysis of differentially expressed genes.Finally,the related gene set files were downloaded from the Sig DB database(https://mail.python.org/)to perform enrichment analysis of CDK1-related functions or pathways.4.We used the CIBERSORT algorithm to evaluate the distribution of 22 immune cells in HCC with high and low CDK1 expression.Common immune checkpoints were downloaded from the Imm Port database(https://www.immport.org/)and their correlation with CDK1 was analyzed.We also evaluated the efficacy of common anti-immune checkpoints(CTLA-4 and PD-1)in CDK1 high and low expression groups,providing a new target for immunotherapy of HCC.Results :1.The results of differential analysis of multiple databases showed that CDK1 was generally highly expressed in pan-cancer,especially in hepatocytes.2.Survival analysis showed that CDK1 was generally associated with the survival and prognosis of patients with hepatocellular carcinoma.High expression of CDK1 was significantly associated with poor prognosis and tumor grading and staging.3.The results of enrichment analysis showed that CDK1 was involved in the progression of hepatocellular carcinoma by affecting cell composition(such as chromosome,synaptic membrane,etc.),biological functions(such as cell proliferation,chromosome separation,etc.)and chemical pathways(such as neuroactive ligand-receptor interaction,cell cycle pathway,etc.).4.The expression level of CDK1 was confirmed to be related to tumor immune infiltration and immune checkpoint,especially with CD276,TNFSF4,PDCD1 and so on.It also revealed that anti-CTLA-4 is a feasible solution for the treatment of hepatocellular carcinoma with low expression of CDK1.Conclusion :CDK1 is highly expressed in hepatocellular carcinoma and is significantly associated with poor survival and prognosis.CDK1 can promote tumor progression through a variety of biological functions,chemical pathways,and immune infiltration,and is a potential target for the treatment of hepatocellular carcinoma.