Background/Aim: Autophagy and immunity play important roles in the growth of malignant tumors and are promising targets for tumor therapy. This study was conducted to identify differentially expressed immune genes related to autophagy in Wilms’ tumor (WT) and analyze their correlation with the disease prognosis. Materials and Methods: The public data of WT and normal kidney tissues were downloaded from TCGA, ImmPort, and GeneCards databases to obtain differentially expressed immune genes associated with autophagy. Survival analysis, ROC curve, and clinical relevance filtering were used to screen the key gene plasminogen activator urokinase (PLAU). The univariable and multivariable Cox regression model analyses were used to analyze the prognostic factors of overall survival (OS) in patients with WT. Then, GO enrichment, KEGG pathway analysis and GSEA were used to enrich and analyze differentially expressed genes. The relationship between PLAU gene expression and tumor microenvironment and infiltration of immune cells was analyzed, as well as between the expression of PLAU and epigenetic modifications. Results: PLAU gene expression was associated with survival and prognosis in WT patients and was an independent prognostic indicator of OS in patients. The GO, KEGG, and GSEA analysis results suggested that PLAU may be involved in RNA transcription and epithelial cell migration. High expression of PLAU was also associated with increased immune cell infiltration and a higher presence of antitumor immune cells. The low expression of PLAU in WT was related to DNA methylation and may be also co-regulated by miR-342-3p. Conclusion: PLAU can be used as an independent prognostic biomarker for WT. Low expression of PLAU is associated with poor prognosis in WT patients. Evidence on the prognostic value of PLAU gene and the pathways that may be associated with its expression is invaluable for the development of new therapies for WT.

Background: To explore the potential role of m6A methylation modification in Wilms Tumor (WT) by m6A-RNA Methylation (m6A) regulators. Methodology: The association of m6A modification patterns with immune and prognostic characteristics of tumors was systematically evaluated using 19 m6A regulators extracted from Wilms Tumor’s samples in public databases. A comprehensive model of “m6Ascore” was constructed using principal component analysis, and its prognostic value was evaluated. Results: Almost all m6A regulators were differentially expressed between WT and normal tissues. Unsupervised clustering identified three distinct m6A clusters that differed in both immune cell infiltration and biological pathways. The m6Ascore was constructed to quantify m6A modifications in individual patients. Our analysis suggests that m6Ascore is an independent prognostic factor for WT and can be used as a novel predictor of WT prognosis. Conclusions: This study comprehensively explored and systematically characterized m6A modifications in WT. m6A modification patterns play a critical role in the tumor immune microenvironment (TIME) and WT prognosis. m6Ascore provides a more comprehensive understanding of m6A modifications in WT and offers a practical tool for predicting WT prognosis. This study will help clinicians to identify valid indicators of WT to improve the poor prognosis of this disease. Supplementary Information: The online version contains supplementary material available at https://www.aliyundrive.com/drive/folder/64be739cd6956a741fb24670baeea53422be6024.

Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT.

Background. To explore the potential role of m6A methylation modification in Wilms Tumor (WT) by m6A-RNA Methylation (m6A) regulators. Methodology. The association of m6A modification patterns with immune and prognostic characteristics of tumors was systematically evaluated using 19 m6A regulators extracted from Wilms Tumor’s samples in public databases. A comprehensive model of "m6Ascore" was constructed using principal component analysis, and its prognostic value was evaluated. Results. Almost all m6A regulators were differentially expressed between WT and normal tissues. Unsupervised clustering identified three distinct m6A clusters that differed in both immune cell infiltration and biological pathways. The m6Ascore was constructed to quantify m6A modifications in individual patients. Our analysis suggests that m6Ascore is an independent prognostic factor for WT and can be used as a novel predictor of WT prognosis. Conclusions.This study comprehensively explored and systematically characterized m6A modifications in WT. m6A modification patterns play a critical role in the tumor immune microenvironment (TIME) and WT prognosis. m6Ascore provides a more comprehensive understanding of m6A modifications in WT and offers a practical tool for predicting WT prognosis. This study will help clinicians to identify valid indicators of WT to improve the poor prognosis of this disease.

Background: Wilms tumor (WT), which is the most common malignancy of the genitourinary system in children. Cuproptosis is a unique form of cell death, and the mechanism of interaction with WT is not yet clear. This study aims at using bioinformatics technology to construct a prognostic signature and identify cuproptosis-related biomarkers to improve the prognosis and treatment of WT. Methods: RNA sequencing and clinical data were downloaded from the TARGET database. The cuproptosis-related lncRNAs were screened by Pearson's correlation calculation, the differentially expressed cuproptosis-related lncRNAs were screened by R software, and a univariate Cox regression analysis was performed on them to screen out the lncRNAs related to prognosis. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a cuproptosis-related lncRNA signature. The predictive ability of the signature was then assessed by Kaplan-Meier (KM) curves, clinically relevant subject acceptance characteristic (ROC) curves, decision curves (DCA), and nomograms. Other clinical factors were further included to verify whether the constructed prognostic signature could be an independent predictor. GO and KEGG functional enrichment analysis was performed on the target lncRNA-related mRNAs to explore their possible functions and pathways involved. Immune infiltration and tumor microenvironment were assessed by CIBERSORT, ESTIMATE, and ssGSEA algorithms to explore potential links between cuproptosis-related lncRNAs related to prognosis. Results: ①A total of 711 cuproptosis-related lncRNAs were screened. ②Through univariate Cox regression analysis, Lasso regression, and multivariate Cox regression analysis, a total of 17 lncRNAs with independent prognostic significance were screened to construct a prognostic signature. ③ The KM survival analysis of the samples by the prognostic signature found that there was a significant difference in survival between the high and low-risk groups, and the high-risk group had a worse prognosis (P<0.01). The area under the time-dependent ROC curve at 1, 3, and 5 years was 0.903, 0.882, and 0.907, combined with other clinical traits to construct the combined index ROC curve, the area under the risk score curve of the prognostic signature was 0.93, indicating that it can be used as an independent prognostic factor independently of other clinical traits. Conclusions: The 17 cuproptosis-related lncRNAs and their prognostic risk signature may be molecular biomarkers and therapeutic targets for the prognosis of Wilms tumor.