Hub Genes and Key Pathway Identification in Wilms Tumor Based on Bioinformatics Analysis

Abstract

Wilms tumor (WT) is a childhood kidney cancer with unknown etiology. Gene expression analysis has become very essential in WT. Thus, we performed an integrated analysis of gene expression data to identify new molecular mechanisms and key functional genes in WT. Gene expression (GSE60850) dataset was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using limma. Pathway and Gene Ontology (GO) enrichment analyses were performed for the DEGs by ToppGene database. Then, protein–protein interaction (PPI) networks and modules were established by the Mentha database and PEWCC1, and visualized by Cytoscape software. Target gene - miRNA regulatory network and target gene - TF regulatory network were established by the Network Analyst database and visualized by Cytoscape software. Finally, survival analysis, expression analysis, stage analysis, mutation analysis, immunohistochemical (IHC) analysis, receiver operating characteristic (ROC), reverse transcription polymerase chain reaction (RT-PCR) and immune infiltration analysis of hub genes was performed. We identified 988 DEGs ultimately including 502 up regulated genes and 486 down regulated genes. Pathway and GO enrichment analysis revealed that DEGs were mainly enriched in D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis, platelet activation, cholesterol biosynthesis III, and complement, coagulation cascades, embryo development, cell surface, DNA-binding transcription factor activity, carboxylic acid metabolic process, extracellular space and signaling receptor binding. FN1, AURKA, TRIM41, NFKBIA, TXNDC5, SIN3A, MAGI1, GPRASP2, UCHL1 and FXYD6 were filtrated as the hub genes. These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of WT and have the potential to be used as diagnostic and prognostic biomarkers or therapeutic targets for WT.