Expression, Functional Enrichment and Signal Pathway Bioinformatic Analysis of FoxO3 Gene in Bladder Cancer
WANG De-xin,QI Feng,LIU Yi-ming
Department of Urology, Beichen Hospital of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300400, China
Abstract:
Objective To investigate the expression of Forkhead box protein O 3 (FoxO3) in bladder cancer,its related biological functions and signaling pathwaysand its relationship with patient survival. Methods The expression level of FoxO3 gene in bladder cancer tissues and adjacent normal bladder tissues were analyzed in TCGA database. STRING database was used to construct the FoxO3 gene-related protein-protein interaction network, cluster analysis of the genes in the network, and Cytoscape was used to screen the key genes in the network. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to enrich the functions of FoxO3 and related genes. Cox regression model was used to construct survival curve and to compare the difference of total survival and disease-free survival between high and low FoxO3 expression groups. Results The expression level of FoxO3 gene in bladder cancer tissues was significantly lower than that in corresponding normal bladder tissues (P <0.05), while the expression level of FoxO3 gene in different clinical stages of bladder cancer tissues had no significant difference (P >0.05). There were 51 protein-protein interaction correlations and 587 protein-protein interaction correlations in the FoxO3 protein-protein interaction network. The average interaction index of each protein was 23, and the protein concentration in the network was obvious (P<1-16).FoxO3 gene expression was positively correlated with FoxO3B gene expression (r =0.94, P <0.05), but negatively correlated with TIMM16 gene expression(r =–0.43, P <0.05). The total survival time (HR=1.4, P = 0.029) and disease-free progression survival(HR = 1.5, P = 0.015) of bladder cancer patients in FoxO3 low expression group were signi?cantly higher than those in high expression group. Conclusion The expression of FoxO3 in bladder cancer tissues is signi?cantly down-regulated, and the low expression of FoxO3 is associated with poor prognosis of bladder cancer patients.