Association between Duchenne muscular dystrophy gene products and prognosis in head and neck cancer

Description

Background
There is growing evidence that the Duchenne muscular dystrophy (DMD) gene plays a role in the development and progression of major cancer types. This study focuses on exploring the prognostic and biological significance of DMD expression in head and neck squamous cell carcinoma (HNSCC).

Methods
Data from The Cancer Genome Atlas (TCGA) were analysed for associations between DMD expression levels and patient outcomes, including overall and progression-free survival. Specific DMD transcripts were evaluated to identify those most strongly associated with survival. Immunohistochemical analysis of dystrophin protein expression was performed in a cohort of 50 HNSCC tissue samples, assessing subcellular localisation and its relationship with clinical outcomes. Functional assays in HNSCC cell lines evaluated the impact of DMD transcript Dp71 variant overexpression on nuclear morphology and cell proliferation. Differential gene expression analysis identified pathways enriched with altered DMD expression.

Results
High DMD expression was associated with improved overall survival (median survival difference: 22 months, p = 0.0083) and progression-free survival (p = 0.0237). Among DMD transcripts, Dp71ab had the strongest link to better overall survival (median survival: 42 months, p = 0.0007). Stratification of HPV+ patients revealed a DMD low/HPV+ subgroup with poorer outcomes. IHC confirmed dystrophin localisation in both the nucleus and cytoplasm, with high nuclear dystrophin expression correlating with longer OS (mean difference: 31 months, p = 0.0497). Functionally, Dp71ab overexpression disrupted nuclear morphology and suppressed cell proliferation. DEG analysis identified pathways associated with muscle processes, ribosome biogenesis, and non-coding RNA regulation.

Conclusions
These findings underscore the potential of DMD as a biomarker for prognosis and therapeutic targeting in HNSCC. The association between Dp71ab expression and improved outcomes, particularly in HPV-positive subgroups, highlights its relevance in stratifying patient risk. Further mechanistic studies of DMD isoforms, particularly Dp71, are warranted to advance our understanding of its function in cancer biology.

Period	Mar 2025
Event title	ESMO Rare Cancers 2025
Event type	Conference
Location	Lugano, SwitzerlandShow on map
Degree of Recognition	International