Identification of disulfidptosis-related molecular subtypes in pleural mesothelioma demonstrates a correlation with the immune infiltration, prognosis and therapy efficacy

Abstract Pleural mesothelioma (PM) is a rare tumor with rising incidence and mortality rates, and limited therapeutic options. Disulfidptosis, a novel phenomenon with significant potential in cancers, lacks clarity of its specific role in PM. We classified molecular subtypes of PM based on disulfidptosis-related genes (DRGs). We firstly identified two novel disulfidptosis-related molecular subtypes in PM. The high-disulfidptosis subtype (Cluster 2) was associated with significantly worse overall survival (HR = 2.24, p < 0.001), an immunosuppressive microenvironment dominated by M2 macrophages, and resistance to immune checkpoint blockade. In contrast, the low-disulfidptosis subtype (Cluster 1) exhibited metabolic reprogramming toward glycolysis and fatty acid oxidation, along with enhanced NK cell infiltration and chemotherapy resistance. Our 11-gene prognostic signature achieved an AUC of 0.95 for 5-year survival prediction. A random survival forest analysis identified LMNB2 and CDCA2 as key attributes, showing elevated expression in cancerous tissues. We propose a new approach to develop personalized treatment strategies through the classification of disulfidptosis related molecular subtypes for PM patients. Novel disulfidptosis-associated biomarkers hold potential as prognostic and therapeutic targets in PM. However, additional research is necessary. Clinical trial number: not applicable.