Integrated Bioinformatics Analysis Of Expression,related Signal Pathways,and Prognostic Significance Of CCNA2 In Hepatocellular Carcinoma

BACKGROUND:Hepatocellular carcinoma(HCC)is one of the most diagnosed malignant carcinomas of the digestive system with a poor prognosis.In this study,the expression of CCNA2 gene expression in HCC was investigated by bioinformatics analysis and the feasibility of CCNA2 gene as a molecular marker for prognosis in HCC was assessed.The results of bioinformatics analysis were verified by immunohistochemistry assay.AIM:To investigate the expression of CCNA2 in HCC,related signal pathways,and its relationship with prognosis.METHODS:The expression levels of CCNA2 m RNA in HCC and paracancerous tissues were compared based on the TCCA database.CCNA2 protein interaction network was constructed based on the String database,and the related protein function and KEGG signal pathways were enriched.According to the expression level of CCNA2,the patients were divided into high and low expression groups,and the difference in overall survival(OS)and disease free survival(DFS)was compared between the two groups.The relationship between the expression of CCNA2 protein analyzed by immunohistochemistry and the clinicopathological features of 72 patients with HCC who underwent surgical treatment was analyzed.RESULTS:The expression level of CCNA2 m RNA was significantly higher in HCC than in normal liver tissues.There are ten proteins that have a close interaction with CCNA2 protein,with edge =50,and the regional clustering index is 0.931.The interaction network of the ten proteins that have a close interaction with CCNA2 protein was significantly enriched(P < 0.05).The expression of TOP2 m RNA was positively correlated with CCNA2expression(r = 0.85,P < 0.05),while CCL14 expression was negatively correlated with CCNA2 expression(r =-0.54,P < 0.05).CCNA2 gene related signaling pathways are mainly enriched in cell cycle,viral carcinogenesis,hepatitis B,p53 signaling pathway,and PI3K-Akt signaling pathway.The prognosis analysis indicated that the OS(HR = 1.7,P = 0.0037)and DFS rates were significantly lower in the high expression group than in the low expression group(HR = 1.6,P = 0.0037).Immunohistochemistry showed that the high expression rate of CCNA2 in HCC was34.7%(25/72).High expression of CCNA2 protein was significantly associated with tumor diameter(P < 0.05),DC infiltration(P < 0.05),and recurrence/metastasis 2years after operation(P < 0.05).CONCLUSION:CCNA2 gene is up-regulated in HCC,which can be used as a molecular marker for poor prognosis in HCC.