| First Author | Wietecha MS | Year | 2023 |
| Journal | Matrix Biol | PubMed ID | 36914141 |
| Mgi Jnum | J:334479 | Mgi Id | MGI:7450609 |
| Doi | 10.1016/j.matbio.2023.03.003 | Citation | Wietecha MS, et al. (2023) Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes. Matrix Biol |
| abstractText | 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. |
