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High-resolution spatial transcriptomics uncover epidermal-dermal divergences in Merkel cell carcinoma: spatial
Kuan Cheok Lei1,2, Nalini Srinivas1,3, Mitalee Chandra1,3
1Translational Skin Cancer Research, German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung - DKTK), Partner Site University Medicine Essen, Essen, Germany.
Oncogene
|October 23, 2025
Summary
Merkel cell carcinoma (MCC) cells in the epidermis adopt a squamous cell carcinoma-like gene expression profile. This keratinocytic differentiation highlights the tumor microenvironment
Area of Science:
- Oncology
- Dermatology
- Cancer Biology
Background:
- Merkel cell carcinoma (MCC) is an aggressive skin cancer with high cellular plasticity and rapid therapy resistance.
- Epidermal localization of MCC is rare, but epidermotropic MCC offers a unique model to study microenvironmental influences.
- The tumor microenvironment significantly impacts cancer cell behavior and aggressiveness.
Purpose of the Study:
- To investigate the transcriptomic profiles of epidermotropic MCC cells.
- To compare epidermotropic MCC cells with those in the tumor core and near blood vessels.
- To understand how the epidermal microenvironment influences MCC cell differentiation and behavior.
Main Methods:
- High-definition spatial and single-cell transcriptomics were employed.
- Gene expression profiles of epidermotropic MCC cells were dissected.
- Comparisons were made between epidermotropic MCC cells, tumor core cells, and perivascular cells.
Main Results:
- Epidermotropic MCC cells display a transcriptomic signature similar to cutaneous squamous cell carcinoma.
- Upregulation of genes encoding keratins, S100A proteins, and calmodulin-like proteins 3 and 5 was observed.
- This keratinocytic differentiation is linked to increased p63 activity and PERP upregulation.
Conclusions:
- Merkel cell carcinoma cells can undergo keratinocytic differentiation in response to epidermal microenvironmental cues.
- This demonstrates the significant phenotypic plasticity of MCC.
- The tumor microenvironment plays a crucial role in shaping tumor cell characteristics in MCC.
