基于多组学分析的尿路上皮癌预后生物标志物及其免疫微环境调控机制研究OA

Objective To conduct a detailed molecular analysis of urothelial carcinoma(UC)using bioinformatics tools,screen for prognosis-related biomarkers,and analyze their relationship with immune cells,so as to provide new insights for the clinical treatment of UC patients.Methods Three gene expression datasets(GSE32548,GSE32894,GSE48075)were obtained from the GEO database.Differentially expressed genes(DEGs)were screened using NetworkAnalyst,and GO/KEGG enrichment analyses were performed using DAVID and Metascape.Hub genes were screened using STRING and Cytoscape.The ONCOMINE,GEPIA,UALCAN,cBioPortal,and HPA databases were used to analyze alterations at the DNA level and expression differences at the mRNA and protein levels of hub genes in UC.The GEPIA and UALCAN databases were used to explore survival differences of hub genes in UC.The TIMER database was used to analyze immune cell infiltration patterns.Results A total of 63 DEGs were screened through the NetworkAnalyst website,including 31 upregulated genes and 32 downregulated genes.GO/KEGG pathway analysis revealed that DEGs were mainly enriched in collagen catabolic process,extracellular matrix organization,and extracellular matrix structural constituents,which were involved in the occurrence,development,and metastasis of UC.Five hub genes(COL1A1,COL1A2,COL3A1,MMP9,and POSTN)were screened using STRING and Cytoscape.cBioPortal database showed that 35%of UC patients had genetic alterations in hub genes,with amplification and deep deletion mutations being the most common.ONCOMINE and UALCAN databases showed that mRNA expression of all hub genes in invasive UC was significantly higher than in superficial UC and normal tissues.HPA database showed that protein expression levels of COL3A1 and POSTN in UC tissues were higher than in normal tissues.GEPIA showed that COL1A2 and COL3A1 were positively correlated with overall survival of UC patients(P<0.05).UALCAN showed that UC patients with high expression of COL1A1,COL1A2,and POSTN had a poorer prognosis(P<0.05).TIMER database revealed significant correlations between hub gene expression and the infiltration of CD4+T cells,CD8+T cells,macrophages,neutrophils,and dendritic cells(P<0.05).Conclusion Five hub genes(COL1A1,COL1A2,COL3A1,MMP9,and POSTN)are screened through bioinformatics analysis,which play key roles in the pathogenesis and progression of UC.The expression of hub genes not only has the potential to serve as prognostic indicators for UC,but also is significantly correlated with the degree of immune cell infiltration in UC.