Objective:To investigate the expression level and clinical significance of cellular communication network factor 4 (CCN4) gene in hepatocellular carcinoma (HCC) based on bioinformatics.Methods:The expression level of CCN4 protein in HCC tissues and its relationship with clinicopathological parameters were analyzed by TCGA database. The correlation between the expression of CCN4 protein and tumor purity and immune cell infiltration was analyzed by TIMER database. Kaplan-Meier Plotter database was used to analyze the relationship between the expression of CCN4 protein and clinical prognosis in HCC. Protein-protein interaction (PPI) network was constructed by using STRING database, and the correlation between proteins was assessed. The relationship between CCN4 expression and clinicopathological parameters was analyzed by Chi-square test. Correlation analysis was conducted by Spearman's rank correlation.Results:Clinical information and corresponding RNA sequencing data of 371 patients were obtained from TCGA HCC dataset. Data analysis showed that the expression of CCN4 protein in HCC patients was correlated with race, T stage and pathological G grade (χ2=9.055, 14.012, 17.163; P<0.05). Kaplan-Meier Plot demonstrated that HCC patients with high expression of CCN4 obtained shorter overall survival (HR=1.50, 95%CI: 1.05-2.14, P<0.05). TIMER database analysis showed that the expression level of CCN4 in HCC was negatively correlated with tumor purity (rs=-0.397, P<0.05), whereas positively correlated with the infiltration levels of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells and M2 macrophages (rs=0.306, 0.279, 0.460, 0.490, 0.465, 0.404, 0.532; P<0.05). PPI network analysis indicated that decorin was the main protein interacting with CCN4 (score=0.953).Conclusions:The expression level of CCN4 protein is associated with race, T stage and pathological G grade, which can be used as a biomarker for poor prognosis of HCC. The underlying mechanism may be related to the infiltration of immune cells, the polarization of M2 macrophages and the formation of stromal fibers.
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