Identification of CDC20 as a Novel Biomarker in Diagnosis and Treatment of Wilms Tumor

Abstract

Objective: Wilms tumor (WT) is a common malignant solid tumor in children. Many tumor biomarkers have been reported; however, there are poorly targetable molecular mechanisms which have been defined in WT. This study aimed to identify the oncogene in WT and explore the potential mechanisms.Methods: Differentially expressed genes (DEGs) in three independent RNA-seq datasets were downloaded from The Cancer Genome Atlas data portal and the Gene Expression Omnibus database (GSE66405 and GSE73209). The common DEGs were then subjected to Gene Ontology enrichment analysis, protein–protein interaction (PPI) network analysis, and gene set enrichment analysis. The protein expression levels of the hub gene were analyzed by immunohistochemical analysis and Western blotting in a 60 WT sample. The univariate Kaplan–Meier analysis for overall survival was performed, and the log-rank test was utilized. A small interfering RNA targeting cell division cycle 20 (CDC20) was transfected into G401 and SK-NEP-1 cell lines. The Cell Counting Kit-8 assay and wound healing assay were used to observe the changes in cell proliferation and migration after transfection. Flow cytometry was used to detect the effect on the cell cycle. Western blot was conducted to study the changes of related functional proteins.Results: We commonly identified 44 upregulation and 272 downregulation differentially expressed genes in three independent RNA-seq datasets. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggested that cell cycle changes are crucial in WT. The top 15 highly connected genes were found by PPI network analysis. Furthermore, we demonstrated that one candidate biomarker, CDC20, for the diagnosis of WT was detected, and its high expression predicted poor prognosis of WT patients. Moreover, the area under the curve value obtained by receiver operating characteristic curve analysis from paired WT samples was 0.9181. Finally, we found that the suppression of CDC20 inhibited proliferation and migration and resulted in G2/M phase arrest in WT cells. The mechanism may be involved in increasing the protein level of securin, cyclin B1, and cyclin AConclusion: Our results suggest that CDC20 could serve as a candidate diagnostic and prognostic biomarker for WT, and suppression of CDC20 may be a potential approach for the prevention and treatment of WT.

Immune-related gene signature associates with immune landscape and predicts prognosis accurately in patients with Wilms tumour

“…In addition, we assessed the expression of four IRGs among them in three human Wilms tumour cell lines and compared them with a normal renal epithelial cell line, suggesting potential targets for further study. Numerous independent studies have shown the expression level of several single-gene was strongly correlated with the prognosis of WT patients (49)(50)(51)(52). Additional information of comprehensive bioinformatics analysis, clinicopathological factors, and model analysis were needed to further enhance the prediction accuracy of the prognosis.…”

The potential role of CDC20 in tumorigenesis, cancer progression and therapy: A narrative review

“…[51] In renal cancer, CDC20 promotes proliferation by increasing the protein levels of securin, cyclin B1, and cyclin A. [55] In addition, CYP1B1 may promote renal cell proliferation, migration, and invasion, and inhibit apoptosis by inducing CDC20 expression. [56] miR-182-5 overexpression inhibits cell proliferation by directly targeting MALAT-1, then the downregulation of MALAT-1 leads to a decrease in CDC20.…”

“…[56] Suppression of CDC20 slao inhibited migration and resulted in G2/M phase arrest in wilms tumor cells by increasing the expression levels of securin, cyclin B1, and cyclin A. [55] Moreover, several studies have shown that CDC20 knockdown can inhibit the invasion and metastasis of prostate cancer, [74] osteosarcoma, [75] cervical cancer, and ovarian cancer [69] (Table 1).…”