Bioinformatics analysis and validation of CD44 and associated biomarkers in prostate cancer

Prostate cancer (PCa) development is linked to CD44, but its pathogenesis is unclear. This study explored the mechanisms of PCa linked to CD44 through bioinformatics and experimental approaches. Transcriptomic data analysis revealed CD44 localization on chromosome 11 and enrichment in the ribosome pathway. Differential expression analysis identified candidate genes, and two biomarkers—PLA2G4D and SERPINB5—were selected through PPI analysis, machine learning, and expression validation. These biomarkers showed lower expression in low CD44 and knockout groups compared to controls. The ANN model demonstrated high predictive accuracy (Area Under the Curve (AUC) = 0.825). Functional analysis showed PLA2G4D enrichment in the protein export pathway and SERPINB5 in dorsoventral axis formation. Twenty-two differential immune cells were identified, with positive correlations between CD44, PLA2G4D, SERPINB5, and NK cells (p < 0.05). Estradiol was identified as a targeted drug for all three genes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed the downregulation of CD44, PLA2G4D, and SERPINB5 in tumor samples (p < 0.01). This study identified two CD44-related biomarkers, offering new therapeutic avenues and insights for PCa treatment.