A unified model for Duchenne muscular dystrophy gene involvement in cancer: context-dependent tumour suppression and oncogenicity.

Abstract

Evidence implicates the Duchenne muscular dystrophy gene (DMD) in tumorigenesis, but survival trends are inconsistent. To resolve this, we conducted a comprehensive global analysis of DMD expression and survival outcomes across 33 tumour types using bulk RNA sequencing data from The Cancer Genome Atlas. We examined the impact of total DMD, individual transcript and dystrophin-associated protein complex (DAPC) gene expression levels on overall survival using Kaplan-Meier analysis, Cox proportional hazard modelling and pathway analysis. DMD expression was significantly associated with survival in nine cancers after Bonferroni correction (α = 0.0015), with high expression linked to either improved or worsened outcomes depending on cancer type. The most abundant DMD transcript, Dp71ab, mirrored total DMD trends, distinguishing two tumour groups with opposing survival associations. Hierarchical clustering suggests these divergent effects may be linked to a subset of signalling and adhesion-related DAPC components. Our findings indicate that DMD does not act uniformly as an oncogene or tumour suppressor. Instead, we propose a context-dependent dual model whereby high DMD expression is tumour suppressive in aggressive cancers and oncogenic in less aggressive tumours.