Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is the most common complication of radical prostatectomy, and has attracted the attention of the medical community. However, CNI-ED responds poorly to traditional treatments for ED. Hence, this study sought to mine hub biomarkers in CNI-ED and explore its potential mechanisms based on bioinformatics and experimental verification.

Gene expression matrix of CNI-ED was downloaded from the gene expression omnibus (GEO; GSE31247) dataset to identify differentially expressed genes (DEGs). Similarly, the above operation was also performed in GSE10804. Next, CNI-ED disease targets were determined by cross-referencing DEGs in GSE31247 and ED-related genes in the GSE10804, DisGeNET, GenCLiP3, and GeneCards databases. Functional enrichment analyses were performed and protein-protein interaction network was constructed to clarify the biological roles and pathways. We also explored the roles of immunity, m6A, ferroptosis, or cuproptosis in CNI-ED and constructed bilateral cavernous nerve injury model of rats to verify gene expressions.

Fifty-four disease targets of CNI-ED were identified. These targets were related to PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, apoptosis and collagen containing extracellular matrix. ANXA1, SPP1, APOE and ERBB3 were identified as hub biomarkers. We further verified the expression of hub biomarkers in CNI-ED rats and verified their expression differences. As for immunity, ferroptosis, and cuproptosis, our analysis indicated that CNI-ED had nothing to do with them. Only the expression of HNRNPA2B1 and IGFBP3 related to m6A was associated with CNI-ED.

We identified ANXA1, SPP1, APOE and ERBB3 as potential hub biomarkers in CNI-ED rats, and found a certain relationship between m6a and CNI-ED. Our research provides new targets and ideas for the treatment of CNI-ED.