基于生物信息学和CRISPR基因敲除筛选技术探索锌指蛋白28在肝细胞癌中的表达及临床意义OA

Objective To investigate the expression and molecular mechanism of zinc finger protein 28(ZNF28)in hepatocellular carcinoma(HCC).Methods The expression data and related clinical characteristic parameters of ZNF28 in HCC and pan-cancerous tissues were obtained from TCGA database,and the relationship between the expression difference of ZNF28 in cancer tissues and normal tissues and the prognosis was compared.Combined with CRISPR knockout screening and CCLE database,the effect of ZNF28 gene on the proliferation of HCC cells was analyzed and its knockout effect was evaluated.R software and maftools package were used to analyze mutant genes,gene enrichment analysis was used to explore ZNF28-related signaling pathways,and TIMER and CIBERSORT were used to study immune infiltration.Results The expression level of ZNF28 in HCC was higher than that in normal tissues,and its high expression was associated with poor prognosis(P<0.05).After ZNF28 knockout by CRISPR,the growth and proliferation rates of 13 HCC cell lines were decreased.The expression level of ZNF28 in most tumor tissues was higher than that in normal tissues,and was associated with the survival and prognosis of patients with various tumors(P<0.05).Mutation analysis showed that the mutation frequency of TP53 gene was the highest,and ZNF28 might play an important role in HCC by regulating complement and coagulation cascades,metabolic pathways,and neuroactive ligand-receptor interactions.In HCC samples with high ZNF28 expression,immune cells such as regulatory T cells,γδT cells,M0/M1 macrophages and activated mast cells were activated.Conclusion A As a potential molecular marker for HCC diagnosis,ZNF28 may be involved in the occurrence and development of HCC by affecting multiple signaling pathways.