| 描述信息 |
Approximately 30% of non-chronically sun-damaged melanomas originate from nevi, yet the dynamic changes and crucial mechanisms driving the transition from benign nevi to melanoma remain elusive. Here, we performed single-cell transcriptome sequencing on multiple paired tissue sites from 5 patients diagnosed with melanoma arising in congenital melanocytic nevi (CMN), identifying four distinct states of melanocyte subpopulations during the progression from nevi to melanoma, characterized by dynamic changes in their composition, functions, malignancy, and regulatory pathways. In the nevi state, interferon regulatory factor 1 (IRF1) was specifically upregulated in melanocytes, fibroblasts, and endothelial cells (ECs), potentially activating immune surveillance in the microenvironment. This underscores a critical factor in preserving the benign state of nevi and averting malignant transformation. 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 on NK cells could potentially serve as a key factor leading to immune evasion. In malignant melanoma samples, we detected high expression of Midkine (MDK) in melanocytes. It is a pivotal factor that facilitates melanoma invasion and malignant transformation, potentially through interaction with ECs 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 (RNA-seq) data. Our study provides a high-resolution atlas of the malignant transformation of melanoma from nevi and highlights potential targets for further investigation. |
