TOP2A-TTK-KIF2C基因网络在肝细胞癌免疫微环境和靶向治疗中的作用OA

Objective To investigate the expression and prognostic value of the DNA topoisomerase Ⅱ alpha(TOP2A)and its key genes TTK and KIF2C in hepatocellular carcinoma(HCC).We also examined their roles in the immune microenvironment and assessed their potential utility in targeted therapy.Methods To determine gene expression and prognosis,an integrated analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases was performed.A PPI network was constructed,and LASSO-Cox regression was used to screen key genes.Furthermore,immune infiltration and drug sensitivity were analyzed,and molecular docking and immunohistochemistry experiments were performed for validation.Results We found that TOP2A,TTK,and KIF2C were significantly overexpressed in HCC,with TTK and KIF2C being identified as key genes with a risk model AUC of 0.745.Moreover,the high expression of these genes was posi-tively correlated with CD8+T cell infiltration and independently associated with a poor prognosis.Furthermore,mutations were positively correlated with microsatellite instability.Molecular docking confirmed that Sorafenib and other drugs could stably bind to these targets.Conclusion Our findings revealed that the TOP2A-TTK-KIF2C network is abnormally activated in HCC and is closely associated with the immune microenvironment.TTK and KIF2C were identified as potential biomarkers and therapeutic targets for the treatment of HCC.