453 Endovascular progenitors initiate and drive de novo vascularisation in melanoma

Abstract

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression and little is known about their altered expression in cSCC. To elucidate cSCC associated coding and non-coding transcriptomic changes, we performed RNA-seq of 9 cSCCs and 7 healthy skin samples. Differential expression analysis was performed by edgeR. CircRNAs were identified using the find_circ and CIRCexplorer pipelines. Altered expression of 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs was identified. Targets of 519 transcription factors were enriched among DEGs, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development and cSCC malignancy (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were also dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel circRNAs, including skin-enriched circ_IFFO2 and circ_POF1B, were identified. Results from the RNA-seq were further validated in an expanded cohort using NanoString nCounter assays. In conclusion, through deep sequencing approach we have identified a reference set of coding and non-coding transcripts with altered expression in cSCC, which represent potential therapeutic targets or biomarkers.