Background: Wilms tumor (WT) is the most common pediatric kidney cancer, with survival rates exceeding 90% in localized cases. However, advanced or recurrent WT remains difficult to treat due to poor prognosis and limited knowledge of its molecular mechanisms. Gene expression profiling has shown promise in identifying prognostic markers and therapeutic targets. This study aimed to identify key prognostic genes and pathways in WT, construct risk prediction models, and validate their role in tumor progression.Methods: RNA sequencing and clinical data from 136 WT patients were obtained from the TARGET database. Differential gene expression analysis was conducted using GEO datasets GSE11024 and GSE66405 to compare WT and normal kidney tissues. Identified differentially expressed genes (DEGs) underwent Gene Ontology (GO) and KEGG pathway enrichment analysis to explore biological functions and pathways associated with WT progression. Univariate Cox regression was used to assess the association between DEGs and overall survival (OS) and progression-free survival (PFS). LASSO regression models were developed for risk stratification, and model accuracy was evaluated using time-dependent ROC curves. External validation confirmed key hub genes, while functional assays in WT cell lines (WiT-49) assessed the role of GRAMD1A in tumor behavior.Results: A total of 3,395 DEGs were identified, with 1,564 upregulated and 1,831 downregulated genes. Enrichment analyses revealed significant pathways involved in cell cycle regulation and metabolic reprogramming. Six key genes (GRAMD1A, PLXNA3, SPR, EBAG9, RBM47, and RIDA) were associated with both OS and PFS. LASSO models demonstrated strong predictive performance, with GRAMD1A identified as a major risk factor. External validation confirmed differential expression, and functional assays showed that GRAMD1A silencing significantly inhibited WT cell viability, proliferation, migration, and invasion.Conclusions: This study identifies novel prognostic genes and potential therapeutic targets in WT. GRAMD1A, SPR, EBAG9, RBM47, and RIDA play critical roles in WT progression, with GRAMD1A as a key oncogenic factor, offering potential for risk stratification and future therapeutic intervention.

Objective: Treating pediatric osteosarcoma in long bones is challenging due to skeletal immaturity, which restricts the generalizability of insights derived from adult patients. Are there disparities in outcomes? How should surgical protocols be tailored for children of varying ages? What are the specific postoperative complications? A large single-center retrospective cohort study of 345 patients under 14 years old with lower-limb osteosarcoma treated in our department since 2000 was conducted to address these inquiries. Methods: A retrospective analysis of 345 pediatric patients with lower-limb osteosarcoma admitted to our department between 2000 and 2019 was conducted. Clinical and functional outcomes were compared based on age groups, surgical methods, type of prosthesis, and primary tumor location. Patients were divided into the low-age group (≤10 y old) and the high-age group (>10 y old). Overall survival rate (OS), progressionfree survival rate (PFS), and prosthesis survival rate were assessed using Kaplan–Meier curves, nonparametric survival analysis (log-rank test), and Univariate cox regression were used for comparison. The incidence of complications, local relapse rate (LRR), metastasis rate, final limb-salvage, and amputation rate, and Musculoskeletal Tumor Society (MSTS) score of different independent groups were further evaluated using χ ² test or Fisher’s exact test, and t-test was employed to evaluate the measurement data. Results: The average age of the patients was 11.10±2.32 years ranging from 4 to 14 y, with an average follow-up duration of 48.17 months. The 5, 10, and 15-year OS rates were 50.3%, 43.8%, and 37.9%, respectively. The progression-free survival rate was 44.8% at 5 years and 41.1% at 10 years. The final limb salvage rate was 61.45%, while the final amputation rate was 38.55%. The low-age group had a higher amputation rate compared with the high-age group (48.00% vs. 33.18%, P=0.009). The overall LRR was 9.28%, and the incidence of metastasis was 28.99%. The LRR of the limb-salvage group was higher than the amputation group (P=0.004). The low-age group experienced more prosthesis-related complications than the high-age group (P=0.001). The most common prosthesis-related complication in the low-age group was soft-tissue failure, while the periprosthetic infection was most frequent in the high-age group. The high-age group had a higher cumulative prosthesis survival compared with the low-age group (P=0.0097). Modular prosthesis showed better MSTS scores and higher cumulative prosthetic survival than expandable prosthesis in pediatric patients (P<0.05). Conclusion: Limb preservation in pediatric patients becomes increasingly efficacious with advancing age, while consideration of amputation is warranted for younger patients. The prevailing postoperative complications associated with prosthesis encompass soft tissue failure and periprosthetic infection. Younger patients diagnosed with lower limb osteosarcoma exhibit a heightened amputation rate and a greater incidence of prosthesis-related complications.

Polycyclic aromatic hydrocarbons (PAHs), widely emitted through industrial processes and vehicular exhaust, are recognized environmental carcinogens. Although PAH exposure has been linked to various malignancies, the specific molecular mechanisms underlying its involvement in pediatric osteosarcoma remain poorly defined. This study analyzed residential and environmental data from 345 pediatric osteosarcoma patients diagnosed between 2000 and 2019 to explore potential correlations with environmental PAH exposure. A total of 1617 candidate PAH-associated molecular targets were retrieved from bioinformatics databases (PubChem, STITCH, GeneCards, DisGeNET), and core targets were identified using STRING and Cytoscape network analyses. Molecular docking was conducted to assess interactions between selected targets and two major PAH compounds, naphthalene (NAP) and benzo[a]pyrene (BaP). In parallel, serum PAHs-DNA adduct concentrations were quantified in 41 patients, and their associations with residential location and clinical outcomes were examined. The analysis refined the initial candidate list to 14 core molecular targets. Among these, ACTB, EGFR, and JUN were identified as key prognostic genes through survival analysis and machine learning models. These genes were enriched in oncogenic pathways, including the PI3K-Akt signaling pathway. Molecular docking confirmed strong binding affinities between NAP/BaP and the three core targets. Clinically, serum PAHs-DNA adduct levels were significantly higher in patients from highly urbanized areas compared to less developed regions (443.9 pg/mL vs. 146.4 pg/mL, p < 0.0001) and were associated with reduced overall survival (p = 0.0091). This study presents the first systems-level investigation elucidating potential molecular mechanisms linking PAH exposure to pediatric osteosarcoma. The identification of ACTB, EGFR, and JUN as environmentally responsive oncogenic mediators offers a mechanistic framework for future validation. These findings support the utility of computational toxicology in environmental risk assessment and highlight potential molecular targets for the prevention and treatment of pediatric osteosarcoma.