Abstract
Background Disulfidptosis, a newly recognized form of cell death activated by disulfide bond stress, differs from apoptosis, ferroptosis, cuproptosis, and pyroptosis. Understanding its role in prostate cancer is essential for developing tailored therapeutic approaches for managing this condition. Here, we establish the first disulfidptosis-based molecular subtyping framework for prostate cancer (PCa) and identify CCNB2 as a novel regulator of disulfidptosis, revealing its dual role in apoptosis activation and immune microenvironment remodeling. Methods We used consensus clustering to classify disulfidptosis into different subtypes and to study the unique characteristics linked to each one. We also developed a Dis score to measure the severity of each patient's subtype. We compared immune infiltration, pathway enrichment, and survival differences among the subtypes and revealed that the level of the score is significantly associated with the prognosis of PCa.Subsequently, we used Cytoscape software to further filter out hub genes and investigated how these genes influence the progression of PCa and their potential mechanisms through in vitro and in vivo experiments. Results We identified three molecular subtypes associated with disulfidptosis (Cluster A, B, C) and three gene subtypes (GeneCluster A, B, C). Each subtype exhibited a distinct prognosis, level of immune cell infiltration, and biological pathway activation. Notably, Cluster B and GeneCluster B, characterized by elevated disulfidptosis gene expression, were correlated with favorable prognosis. Additionally, we discovered that patients with higher scores exhibited lower tumor mutational burden (TMB) and improved prognosis. Finally, our experimental results confirmed that downregulation of CCNB2 expression promoted disulfidptosis in prostate cancer cells, thereby inhibiting their migration and proliferation capacities. Conclusion This study demonstrates that disulfidptosis can be utilized to stratify risk in patients with PCa. Furthermore, the CCNB2 gene emerges as a potential therapeutic target for prostate cancer by regulating disulfidptosis, thereby influencing the biological behaviors of PCa cells, including their proliferation and migration.