Identification and Validation of Cuproptosis-Related LncRNA Signatures as a Novel Prognostic Model for Wilms Tumor

Abstract

Abstract 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.