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Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental
Qiang Zeng1,2, Tingting Liu1,2, Lilu Qin1
1Department of Pediatric Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, 330100, Jiangxi, China.
Background:
Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.
Methods:
Differential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes' functions in WiT-49 cells.
Results:
The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.
Conclusions:
EMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.
Insights
Researchers identified EMCN and CCNA1 as key prognostic markers for Wilms tumor (WT), a common pediatric cancer. These findings offer potential new therapeutic targets for improving WT patient outcomes by understanding its molecular mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wilms tumor (WT) is the most common pediatric embryonal tumor.
- Its pathogenesis is not well-researched, necessitating further investigation into molecular mechanisms.
- Understanding WT requires exploring gene expression profiles and cellular pathways.
Purpose of the Study:
- To identify molecular mechanisms of Wilms tumor (WT).
- To discover novel prognostic markers for WT.
- To find potential molecular targets for WT therapy.
Main Methods:
- Differential gene expression analysis was performed on WT transcriptomic data from GEO and TARGET databases.
- Gene Ontology (GO) and KEGG pathway enrichment analyses were utilized for functional insights.
- LASSO regression and Cox regression identified and validated prognostic-related hub genes, including EMCN and CCNA1.
Main Results:
- Enrichment analysis revealed significant involvement of differentially expressed genes (DEGs) in angiogenesis and cell differentiation regulation.
- Twenty-four DEGs were identified, with nine found to be prognostic-related in WT patients.
- EMCN and CCNA1 were identified as key hub genes associated with WT progression, and their manipulation affected cancer cell behavior.
Conclusions:
- EMCN and CCNA1 are key prognostic markers in Wilms tumor (WT).
- These genes show potential as therapeutic targets for WT.
- The study highlights significant roles for angiogenesis and cell differentiation in WT pathogenesis.
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