Transcriptome analysis identifies oncogenic tissue remodeling during progression from common nevi to early melanoma

Am J Pathol. 2023 May 3:S0002-9440(23)00134-7. doi: 10.1016/j.ajpath.2023.03.016. Online ahead of print.ABSTRACTEarly detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development involves a stepwise process during which genetic changes drive histological alterations within nevi and surrounding tissue. Here, we perform a comprehensive analysis of publicly available gene expression datasets of melanoma, common or congenital nevi (CN), and dysplastic nevi (DN), and assess molecular & genetic pathways leading to early melanoma. Our results demonstrate several pathways reflective of ongoing local structural tissue remodeling activity likely involved during the transition from benign to early-stage melanoma. These processes include the gene expression of cancer associated fibroblasts (CAF), collagens, extracellular matrix (ECM) and integrins, which assist early melanoma development and the immune surveillance which plays a substantial role at this early stage. Further, we show genes upregulated in dysplastic nevi (DN) are also overexpressed in melanoma tissue, supporting the notion DN may serve as a transitional phase towards oncogenesis. Lastly, we reveal CN collected from healthy individuals exhibit different gene signatures compared to histologically benign nevi tissue located adjacent to melanoma (adjacent nevi, AN). We show the expression profile of micro-dissected AN tissue...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research