A novel model incorporating chromatin regulatory factors for risk stratification, prognosis prediction, and characterization of the microenvironment in Wilms tumor
Xiaodong Zhao, Xiaobin Chu, Lei Song, Weichun Tang- Genetics (clinical)
- Drug Discovery
- Genetics
- Molecular Biology
- Molecular Medicine
Abstract
Background
Wilms tumor, also known as nephroblastoma, a pediatric most‐frequent malignant‐kidney tumor, may be regulated and influenced by transcriptional and epigenetic mechanisms. Chromatin regulatory factors (CRs) play key roles in epigenetic regulation. The present study aimed to explore the involvement of CRs in the development of nephroblastoma.
Methods
RNA‐sequencing and clinical information of nephroblastoma samples were obtained by downloading data from the TARGET database. The Limma package was utilized to perform differential expression analysis of genes (DEGs) between the tumor group and the control group. A Venn map was used for intersection of differential genes and CRs and to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs using the clusterProfiler package. LASSO and Cox analyses were used to construct CR‐related risk models and were evaluated based on clinical parameters. A receiver operating characteristic curve was employed to assess the diagnostic performance of risk model. Furthermore, we used a single‐sample gene set enrichment analysis algorithm for immune cell infiltration analysis. Finally, to confirm the transcriptome expression of pivotal genes in human nephroblastoma cell lines, a quantitative real‐time PCR was employed.
Results
Fifteen key CRs were obtained through analysis in nephroblastoma and then the risk model based on 13 important CRs was constructed using the transcriptome data of nephroblastoma. Using the risk model, pediatric nephroblastoma patients were stratified into high‐ and low‐risk groups based on their individual risk scores. The risk score of CRs can predict adverse outcomes in pediatric nephroblastoma, and this gene cluster is closely related to various immunity characteristics of nephroblastoma. Moreover, the nephroblastoma cell line exhibited higher expression levels of prognostic genes (VRK1, ARNTL, RIT1, PRDM6, and TSPY1) compared to the HEK293 T cell line.
Conclusions
The risk characteristics derived from CRs have tremendous significance in predicting prognosis and guiding clinical classification and intervention strategies for pediatric nephroblastoma.