Hypospadias, a prevalent congenital anomaly affecting patients’ quality of life, remains incompletely understood in terms of its pathogenesis. This study aimed to identify key genes and molecular mechanisms through transcriptome sequencing and bioinformatics analysis. Transcriptome sequencing was conducted on foreskin samples from 15 patients with hypospadias and 15 controls. Differential expression analysis and WGCNA were used to identify differentially expressed genes (DEGs) and key modules. Genes common to both approaches were further analyzed through PPI network filtering, followed by feature selection using LASSO and SVM-RFE algorithms. Hub genes were identified based on an AUC > 0.8. Functional, immune, and regulatory analyses were performed to investigate their biological roles. Three hub genes—CSF3R, SELL, and FCN1—demonstrated significant diagnostic potential (AUC > 0.8). Functional enrichment analysis revealed their association with cytokine receptor interaction and chemokine signaling pathways. Eleven immune cell types, including activated dendritic cells, were found to be elevated in the patient cohort. All hub genes were upregulated in the disease group. CSF3R, SELL, and FCN1 represent potential diagnostic biomarkers for hypospadias and provide valuable insights into its molecular mechanisms and potential therapeutic approaches.
Yao et al. (Sat,) studied this question.