Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation.

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.

Predictive nomograms for risk and prognostic factors in metastatic bladder cancer: a population-based study.

Background: Given the poor prognosis of patients with metastatic bladder cancer (MBC), the development of an effective diagnostic and prognostic model is significant in cancer management and for guidance in clinical practice. Methods: We acquired data of 23,180 bladder cancer patients from Surveillance Epidemiology and End Results (SEER) database registered from 2010 to 2019. The optimal cut-off value for patient age and tumor size was determined by x-tile software. Independent risk factors for MBC were identified by univariate and multivariate logistic regression analyses and prognosis factors were identified by univariate and multivariate cox regression analyses, and risk and prognostic nomograms were constructed. The accuracy of the nomograms was verified by receiver operating characteristic (ROC) curves, calibration curves, and its clinical utility was determined by decision curve analysis (DCA) curves and clinical impact curves (CIC). Kaplan-Meier (K-M) survival curves further confirmed the clinical validity of the prognostic model. Results: Through logistic regression analyses, we derived that age, histological type, tumor size, T stage, and N stage were independent risk factors for metastasis in bladder cancer patients. By cox regression analyses, age, chemotherapy, histological type, bone, lung and liver metastases were identified as risk factors influencing prognosis of MBC patients. Area under the curve (AUC) of the risk nomogram was 0.80, the AUC values of 1/2/3 years were 0.74/0.71/0.71 in the training group and 0.81/0.77/0.77 in the validation group. Based on calibration curves, DCA curves, CIC and K-M curves, the nomograms were validated with excellent predictive performance and clinical utility for MBC. Conclusions: The nomograms we constructed have perfect predictive accuracy and clinical practicality for MBC patients, enabling clinicians to provide treatment advice and clinical guidance to patients.