Abstract
Approximately 30% of nonchronically sun-damaged melanomas originate from nevi, yet the dynamic changes and crucial mechanisms driving the transition from benign nevi to melanoma remain elusive.
In this study, we performed single-cell transcriptome sequencing on multiple paired tissue sites from five patients diagnosed with melanoma arising in congenital melanocytic nevi, identifying four distinct states of melanocyte subpopulations during the progression from nevi to melanoma, characterized by dynamic changes in their functions and regulatory pathways.
In the nevi state, IFN regulatory factor 1 was specifically upregulated in melanocytes, fibroblasts, and endothelial cells, potentially activating immune surveillance in the microenvironment. Conversely, the critical inhibitory checkpoint HLA-E for NK cells exhibited high expression in a cluster of malignant melanocytes and fibroblasts enriched in melanoma. This interaction with ligands expressed in NK cells could potentially serve as a key factor, leading to immune evasion. In malignant melanoma samples, we detected high expression of midkine in melanocytes. It is a pivotal factor that facilitates melanoma invasion and malignant transformation, potentially through interaction with endothelial cells to stimulate angiogenesis. The targets identified in our study are crucial factors in detecting the malignant transformation of nevi. Ultimately, we developed a malignant progression model capable of predicting patient prognosis and malignant progression status using bulk RNA sequencing data.
Our study provides a high-resolution atlas of the malignant transformation of melanoma from nevi and highlights potential targets for further investigation.
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