Skin of color associated genes with worse outcomes in cutaneous squamous cell carcinoma

Summary: Abstract Body: There is a paucity of controlled studies examining racial disparities in treatment and outcome in cutaneous squamous cell carcinoma (cSCC) patients despite being well reported in highly prevalent cancers.1-3 We previously reported poor cSCC outcomes in skin of color (SOC) compared to non-Hispanic white (NHW) patients and separately reported canonical genes that drive aggressive behavior in cSCC.4 To elucidate the underlying mechanisms for SOC patient poor outcomes, we performed transcriptomic analysis using a custom cSCC specific 183 Nanostring platform on SOC (N=44) and NHW (N=186) samples. We performed differential and functional enrichment analysis (FEA). We identified 56 differentially expressed genes (DEGs) in SOC and NHW samples. There were 28 DEGs between metastasis and non-metastasis SOC samples including CSMD3, COL25A1, KSR2, PLA2G6, LAMA2, and PCSK1. FEA was performed on the 56 SOC-associated DEGs and identified downregulated pathways of cell cycle/cell division and upregulation pathways of keratinization and metabolism. We performed 2-D unsupervised hierarchical clustering analysis including 3-factors (SOC vs NHW, tumor risk, and metastatic status) on the 56 DEGs and identified 4 distinct clusters. FEA was performed and identified distinct clusters in cell division/differentiation, muscle processes, metabolism, and keratinization. Additionally, we performed FEA on the 28 genes associated with metastasis in SOC samples and identified the down-regulation of metabolic and catabolic pathways. We identified DEGs in SOC cSCC as well as defined enriched pathways of disease. A subset of DEGs were associated with poor outcomes previously reported as predictive of metastasis and survival.4 Zachary Leibovit-Reiben¹, Alyssa L. Stockard¹, Alysia Hughes¹, Xing Li², Javier Canueto³, Collin Costello¹, Aaron R. Mangold¹ 1. Dermatology, Mayo Clinic Arizona, Scottsdale, AZ, United States. 2. Health Sciences Research, Mayo Clinic Minnesota, Rochester, MN, United States. 3. Dermatology, Complejo Asistencial Universitario de Salamanca. Salamanca (Spain), Salamanca, Spain. UV Biology/Injury and Non-melanoma Cancers