A disulfidptosis-related gene signature predicts overall survival in mantle cell lymphoma independently of proliferation

Abstract Objectives Disulfidptosis is a recently defined form of regulated cell death driven by aberrant disulfide bonding in actin cytoskeleton proteins during glucose starvation and high cystine import. To our knowledge, its relevance in mantle cell lymphoma (MCL), a clinically heterogeneous B-cell malignancy, has not been examined. Methods Using publicly available microarray data (GSE93291; 123 MCL patients with overall survival, Affymetrix GPL570), we characterized 13 canonical disulfidptosis-related genes (DRGs). A six-gene LASSO-Cox score was constructed, evaluated by Kaplan–Meier analysis and time-dependent ROC, internally validated by bootstrap optimism correction, and tested for independence from a proliferation score in a multivariable model. Results Seven DRGs were individually prognostic; notably, SLC7A11 , the cystine transporter central to disulfidptosis, was not (hazard ratio [HR] = 1.14; p=0.36), whereas cytoskeletal genes carried the signal. The six-gene score ( SLC3A2 , MYH9 , MYH10 , FLNB , MYL6 , DSTN ) separated two groups with markedly different survival (HR=4.28; 95 % CI=2.38–7.70; log-rank p=1.8 × 10 −7 ). Discrimination held after bootstrap correction (apparent C-index, 0.76; corrected, 0.72). The score was uncorrelated with proliferation (r=0.14) and remained prognostic after adjustment (likelihood-ratio p=3.9 × 10 −12 ). Conclusions To our knowledge, this is the first description of disulfidptosis-related gene expression in MCL, suggesting the prognostic signal is cytoskeletal rather than transporter-driven and distinct from proliferation. As no independent public MCL cohort with survival was available, external validation could not be performed and remains an essential next step.