Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes

Abstract

Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time course of healing. Their comparison to cancer transcriptomes revealed that a resolution-phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early-wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late-wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer.

Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization

“…Millions of patients suffer from regenerative deficiencies, such as refractory wound healing [ 1 ], around the world. Different therapeutic strategies for refractory wound healing have been developed in recent decades [ 2 ]. The most commonly used therapeutic strategies are growth factor dressing [ 3 ] and stem cell therapy [ 4 ].…”