Spatial and Single-cell Transcriptomics Reveal Oncofetal Reprogramming of Fibroblasts is Associated with Malignant Degeneration of Burn Scar

Mechanisms driving malignant degeneration of burn scars remain elusive. While wound healing was traditionally seen as concluding with matrix remodeling, it is now understood as "activated fibrosis" where scars evolve from sustained inflammation ( Foster et al., 2021 Foster D.S. Januszyk M. Yost K.E. Chinta M.S. Gulati G.S. Nguyen A.T. et al. Integrated spatial multiomics reveals fibroblast fate during tissue repair. Proceedings of the National Academy of Sciences. 2021; 118 Crossref Scopus (74) Google Scholar ). Recent work has shown that extracellular matrix regulates regional competence for tumorigenesis ( Bansaccal et al., 2023 Bansaccal N. Vieugue P. Sarate R. Song Y. Minguijon E. Miroshnikova Y.A. et al. The extracellular matrix dictates regional competence for tumour initiation. Nature. 2023; : 1-8 Google Scholar ). This prompts an evaluation of whether immunity and scar matrix drive Marjolin's ulcer (MU), a highly aggressive skin cancer that most commonly arises in non-healed burn wounds or established burn scars. MU is most commonly squamous cell carcinoma (SCC) with metastasis rates up to 40% with ∼50% recurrence and ∼50% 5-year survival ( Khan et al., 2020 Khan K. Schafer C. Wood J. Marjolin ulcer: a comprehensive review. Advances in Skin & Wound Care. 2020; 33: 629-634 Crossref Scopus (19) Google Scholar ).