Integrated bioinformatic analysis identifies COL4A3, COL4A4, and KCNJ1 as key biomarkers in Wilms tumor

Abstract

Wilms tumor (WT) is one of the most common pediatric solid tumors, affecting 1 in 10,000 children, worldwide. A subset of WT patients has poor prognosis, which is associated with a high risk of advanced and/or recurrent disease. Therefore, candidate markers are urgently needed for the diagnosis and effective treatment of WT. We evaluated three mRNA microarray datasets to identify the differences between normal kidney tissue and WT tissue. Gene expression profiling revealed 130 differentially expressed genes (DEGs). Enrichment analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs. Subsequently, we established a protein-protein interaction (PPI) network to reveal the associations among the DEGs and selected 10 hub genes, all of which were downregulated in WT. The expression of COL4A3, COL4A4, KCNJ1, MME, and SLC12A1 in WT tissues was significantly lower than that in normal renal tissues. Survival analyses using the Kaplan-Meier method showed that patients with WT and low expression of COL4A3, COL4A4, and KCNJ1 exhibited remarkably poor overall survival. The correlations among COL4A3, COL4A4, and KCNJ1 in WT were analyzed using cBioPortal; COL4A3, COL4A4, and KCNJ1 were positively correlated with each other. Thus, these genes were considered clinically significant and might therefore play important roles in carcinogenesis and the development of WT.