Melanoma on Chronically Sun-Damaged Skin: Deciphering Gene Expression Signatures

Abstract

Introduction: Melanoma of the skin is responsible for most skin cancer-related deaths. It is well known that exposure to ultraviolet radiation is the most common and modifiable risk factor for melanoma.  Melanomas arising on chronically sun-damaged skin have shown a higher mutational burden.

Objective: We sought to analyze skin samples of patients with melanoma on chronically sun-damaged skin (CSDS) to identify possible gene expression signatures that may contribute to melanomagenesis.

Methods: Design: Experimental. Participants: A total of 10 subjects with a newly diagnosed melanoma on CSDS. Eligibility criteria included patients older than 18 years old with a recent diagnosis of melanoma on CSDS. Intervention: For each patient, 2 skin samples were obtained using a 2-mm punch (1 from CSDS within 2 cm of the primary melanoma, another from sun-protected skin). Skin samples were sent to the Sylvester Onco-genomics Core for library preparation and RNA sequencing. Main Outcomes: Identification of differentially expressed genes between CSDS and non-CSDS of melanoma patients.

Results: Significant differences were observed between the CSDS and non-CSDS samples. Pathways involved in inflammation (e.g., IL-17 signaling), immune responses (e.g., ABC transporters), and oxidative phosphorylation were overexpressed in CSDS.

Conclusions: CSDS can be an adequate milieu for the development and progression of melanoma. CSDS reveals overexpression of pathways involved in inflammation, immune responses, and oxidative phosphorylation, which may facilitate interactions between the skin microenvironment and melanocytes/melanoma cells, predisposing to melanoma development and progression.