Track: Clinical Studies

Abstract:

Melanoma can often be difficult to diagnose, as some cases resemble benign moles (melanocytic nevi). As one of the deadliest forms of skin cancer, early treatment and diagnosis is imperative to reduce morbidity and mortality. Early melanoma is contained within the uppermost layer of the skin (epidermis), which is rich in keratinocytes. However, research focusing on the role of epidermal keratinocytes in melanoma progression is lacking. Additionally, keratinocytes may be a potential source of biomarker discovery, which can help achieve an accurate diagnosis. In this study, we used single-cell spatial transcriptomics to profile the in-situ expression of ~6000 genes within 147,541 individual cells of the keratinocyte microenvironment of 7 melanocytic tumors (3 invasive melanomas, one melanoma in situ, one dysplastic nevus, one common nevus) and one basal cell carcinoma. Sections of lesional and adjacent non-lesional epidermal tissue were included in each analysis. A differential gene expression analysis between the lesional and non-lesional keratinocytes clusters revealed an upregulation of the damage associated molecular patterns (DAMPs) S100A7, S100A8, and S100A9 and wound-associated keratins (KRT6B and KRT6C) in the keratinocyte microenvironment of melanoma and basal cell carcinoma, but not nevi. Additionally, expression of DSC2, DYNLL1, LCN2 and RAB11A was found to be uniquely upregulated in the keratinocyte microenvironment of each melanoma sample. Ultimately, our research reveals a keratinocyte population within the microenvironment of melanoma with a unique gene signature and highlights the potential biomarkers and therapeutic targets within this keratinocyte population.

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Maayan Baron