BACKGROUND: Malignant rhabdoid tumor of the kidney (MRTK) is a rare type of tumor that lacks typical clinical manifestations. Herein, we presented clinical data of 2 children with MRTK. In addition, we used a high-throughput RNA-sequencing (RNA-seq), GO analysis, and KEGG signaling pathway analysis to examine gene expression differences at the transcripts level between 2 patients with MRTK and 3 patients with non-tumor diseases without other symptoms.
METHODS: Preoperative B-scan ultrasonography and computed tomography (CT) examination in 2 cases suggested nephroblastoma. Both patients were treated with radical nephrectomy. After the operation, MRTK was confirmed by pathological examination. Child 1 and Child 2 then received 7 courses and 12 courses of regular chemotherapy, respectively. Child 1 was followed up for 2 years, and Child 2 for 3.1 years without showing symptoms. RNA-seq results showed 2203 differential genes (DEGs) in the kidney tissue of children with MRTK compared to normal tissue (p <0.01). GO analysis suggested that most DEGs participate in protein binding. KEGG results showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway and microRNA-related proteins.
CONCLUSIONS: The PI3K-Akt signaling pathway and microRNA-related proteins as targets have extremely high potential value for the diagnosis and treatment of MRTK.

Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.