Integrated Analysis of the lncRNA-Associated ceRNA Network in Wilms Tumor via TARGET and GEO Databases

Abstract

Wilms tumor (WT) is the most common genitourinary renal tumor that typically occurs in children under 15 and is thought to be linked to somatic and germline mutations. However, the specific functional role of competing endogenous RNAs (ceRNAs) and their potential implications in WT remain unclear. In this study, we developed an lncRNA-mediated (long noncoding RNA-mediated) ceRNA network via the R packages for WT with expression data obtained from the tumor alterations relevant for genomics-driven therapy (TARGET) database. Unsupervised hierarchical clustering analysis revealed that the WT specimens could be clearly distinguished from healthy specimens with respect to the expression of disordered RNAs. A total of 1,607 differentially expressed (DE) lncRNAs, 116 DE microRNAs (DEmiRNAs), and 3,262 DE messenger RNAs (DEmRNAs) were identified as WT-specific RNAs, and a lncRNA-miRNA-mRNA ceRNA network with 159 DElncRNAs, 18 DEmiRNAs, 131 DEmRNAs, and 792 interactions was constructed. According to the clinical survival data, 12 DElncRNAs, 5 DEmRNAs, and 2 DEmiRNAs were selected from the ceRNA network that could significantly impact the overall survival of WT patients ( $P<0.05$ ). Functional enrichment analysis showed that the biological processes and pathways of DEmRNAs, such as cell cycle and virus infection, may be associated with WT. The present study constructed a dysregulated lncRNA-mediated ceRNA network in WT and discovered that lncRNA-mediated ceRNAs may serve as important regulators in WT development and progression. Survival-associated RNAs may serve as new potential biomarkers, suggesting that the constructed ceRNA network in WT might be important for determining optimal therapeutic strategies.