| Part ?: To isolate the hepatocellular carcinoma related genes by The Cancer Genome Atlas and analyze them with bioinformatics methods.Objective : To explore the correlation between the expression of CDK1 mRNA in the tissues of patients with hepatocellular carcinoma and its clinical characteristics and prognosis,in the hope of providing a new target for the targeted treatment of hepatocellular carcinoma.Methods: This study performed a comprehensive analysis of the expression data of 423 HCC patients(373 tumors and 50 controls)downloaded from The Cancer Genome Atlas(TCGA).The most significant top 100 up-regulated gene signatures and top 100 down-regulated gene signatures were identified by using R software combined with edge R package(log FC >2 fold,P<0.05).Gene Ontology(GO)enrichment analysis and pathway analysis of those genes were performed based on Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes(KEGG).Protein-protein interaction(PPI)network was constructed.Results: We screened 15508 gene signatures,of which 7010 up-regulated,8498 down-regulated.The top 100 up-regulated and top 100 down-regulated gene signatures were selected for further research.GO enrichment analysis showed 20 items(FDR<0.01)indicating that these gene biological pathways are mainly enriched in sister chromatid cohesion,cell division,mitotic nuclear division,G2/M transition of mitotic cell cycle,chromosome segregation,G1/S transition of mitotic cell cycle,anaphase-promoting complex-dependent catabolic process,mitotic metaphase plate congression,protein localization to kinetochore,mitotic sister chromatid segregation.Cell localization mainly focuses on chromosome,centromeric region,midbody,condensed chromosome kinetochore,condensed chromosome outer kinetochore,Kinetochore,spindle microtubule,spindle midzone,spindle,condensed nuclear chromosome outer kinetochore,Ndc80 complex.KEGG pathway analysis involved 9 pathways(P<0.01)and were mainly in the cell cycle,Oocyte meiosis,Progesterone-mediated oocyte maturation,HTLV-I infection,p53 signaling pathway,MicroRNAs in cancer and other signaling pathways.PPI network suggested that the central node has Cyclin Dependent Kinase 1(CDK1),Cyclin B1(CCNB1),Cyclin B2(CCNB2),Cell Division Cycle 20(CDC20),Polo Like Kinase 1(PLK1),BUB1 Mitotic Checkpoint Serine/Threonine Kinase(BUB1),etc.Conclusion: Our study displayed that the occurrence of HCC may be associated with abnormal mitotic.Besides,genes CDK1,CCNB1,CCNB2,CDC20,PLK1,BUB1 and others might play important roles for the occurrence and progression of HCC.Part ?: Expression and Clinical Significance of CDK1 in Patients with HCCObjective: To explore the correlation between the expression of CDK1 mRNA in the tissues of patients with hepatocellular carcinoma and its clinical characteristics and prognosis,in the hope of providing a new target for the targeted treatment of hepatocellular carcinoma.Methods: In this study,we attempted to assess the independent prognostic value of CDK1 in terms of overall survival(OS)through a retrospective study based on data from the cancer genome atlas(TCGA)liver and hepatocellular carcinoma(LIHC)cohort.The gene expression profile and related clinical data of HCC tissue samples were collected,and these samples were divided into low CDK1 expression group and high CDK1 expression group.The expression of CDK1 and related clinical information were analyzed.The t-test was used for comparison of continuous data between groups;the chi-square test was used for comparison of categorical data between groups;the log-rank(Mantel-Cox)test was used for survival analysis;the Cox proportional hazards model was used for univariate and multivariate analyses of survival data.Results:1.The primary HCC tissues(N=371)had significantly elevated CDK1 expression than normal liver tissues(N=50).CDK1 expression was higher in HCC tissues(N=50)than in paired adjacent normal tissues(N=50).we adopted the Oncomine database to further validate the expression of CDK1 in HCC vs normal.2.The expression level of CDK1 mRNA was significantly correlated with the difference in the survival status of patients with histological grading of clinical stage recurrence(P<0.05),but was not significantly correlated with the gender of patients with liver fibrosis,Ishak score and liver function Child-pugh graded residual tumor(P>0.05).3.Univariate analysis of survival data showed that the overall survival rate after hepatocellular carcinoma surgery was significantly correlated with the clinical stage and CDK1 mRNA expression level of the patients(P<0.05),but was not significantly correlated with the age and gender of the patients,liver fibrosis Ishak score,liver function Child-pugh grading,and histological grading of residual tumor(P>0.05).4.Multivariate analysis of survival data showed that clinical staging(HR:2.272,95%CI :1.559-3.310,P<0.001)and CDK1 mRNA expression(HR:1.287,95%CI :1.071-1.547,P=0.007)were independent risk factors for the prognosis of HCC patientsConclusion:1.Based on these findings,we infer that CDK1 was overexpression in hepatocellular carcinoma tissues and its expression level was closely related to the survival status of patients with histological grading,clinical stage and recurrence status.2.CDK1 mRNA expression can be an independent risk factor for prognosis of hepatocellular carcinoma patients. |
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