Learning Objective: At the conclusion of this presentation, the participants should be able to discuss keloid fibroblast differential gene and protein expression in responders versus non responders using spatial gene and protein expression.
Objective: Keloid disease (KD) is characterized by benign fibroproliferative skin tumors with high recurrence rates. Fibroblasts are responsible for the keloid phenotype, however, molecular differences between responders and non-responders are unknown. The objective of this study is to compare keloid fibroblast gene expression in responders and non-responder using spatial gene and protein expression in a primary untreated formalin fixed paraffin embedded (FFPE) cohort.
Study Design: Retrospective FFPE cohort.
Methods: One tissue micro array slide comprised of punch biopsies of primary untreated keloids adjacent normal tissues from the head and neck area was created, following the nanoString® DSP Technology Access Program protocol. The GeoMx Human Whole Transcriptome Atlas and Next Generation Sequencing Protein Assays were performed, using morphology marker FAP. Polygonal region of interests (ROI) selection strategy for Fibroblast Activation Protein (FAP) positive cells was conducted.
Results: Thirteen areas of interest (AOIs) were analyzed. 18,676 genes across 13 AOIs were assayed. 3,325 and 1,649 genes expressed in 10% and 50% of AOIs, respectively. A panel of 77 proteins were assayed. Principle component analysis (PCA) demonstrated normal region case-specific genomic variation and keloid region clustering with defined differences between responders and non-responders. Pathway analysis of differential gene expression identified responder and non-responder specific biological processes. In addition, responder and non-responder were found to have differential protein expression.
Conclusions: Spatial analysis identified differential gene and protein expression in keloid fibroblasts of responders and non-responders