ArticleDiscover oncology2026
Identification of disulfidptosis-related molecular subtypes in pleural mesothelioma demonstrates a correlation with the immune infiltration, prognosis and therapy efficacy.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPleural mesothelioma (PM) is a rare and aggressive malignancy with increasing incidence, high mortality, and limited treatment options. Disulfidptosis, a newly identified form of regulated cell death, may play an important role in cancer, but its relevance in PM remains unclear.
methodsTranscriptomic and clinical data of PM were obtained from public databases. PM was classified into molecular subtypes based on disulfidptosis-related genes (DRGs). We then compared prognosis, tumor microenvironment, metabolic features, predicted response to immune checkpoint blockade, and chemotherapy sensitivity between subtypes. In addition, a prognostic signature was established, and key genes were identified using random survival forest analysis.
resultsTwo novel DRG-defined molecular subtypes were identified in PM. The DRGs-high subtype (Cluster 2) was associated with significantly worse overall survival, an immunosuppressive microenvironment dominated by M2 macrophages, and a lower predicted likelihood of response to immune checkpoint blockade. In contrast, the DRGs-low subtype (Cluster 1) showed metabolic reprogramming toward glycolysis and fatty acid oxidation, increased NK cell infiltration, and reduced sensitivity to chemotherapy. An 11-gene prognostic signature demonstrated predictive performance, with an AUC of 0.95 for 5-year survival (95%CI 0.881-1.013). Random survival forest analysis identified LMNB2 and CDCA2 as key genes, both of which were highly expressed in tumor tissues.
conclusionsPM can be classified into two DRG-defined molecular subtypes with distinct prognostic, immune, and metabolic features. These findings provide insights into PM heterogeneity and may support future studies on therapeutic stratification. The prognostic signature remains exploratory and requires validation in independent external cohorts before clinical application.
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