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Decoding the complexity of skin cancer with single cell sequencing

Decoding the complexity of skin cancer with single cell sequencing

May is Skin Cancer Awareness Month. Most skin cancers are caused by skin damage that happens from exposure to ultraviolet (UV) light from the sun. All types of skin are at risk of sun damage and skin cancer with fair-skinned people being affected most often.

Skin cancers are the most common groups of cancers diagnosed worldwide, with more than 1.5 million new cases estimated in 2020. The two broad categories of skin cancer are melanoma and non-melanoma. The most common, non-melanoma types are basal cell carcinoma and squamous cell carcinoma.

Read our blogpost summarizing the latest research in the skin cancer field that utilized single cell sequencing in order to better understand the skin cancer tumor microenvironment and the prognostic signatures of different types of skin cancers.

Ferroptosis-related prognostic signature for melanoma

Ferroptosis is a newly emerging form of iron-dependent regulated cell death that plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy. Liu and colleagues (1) identified a ferroptosis-related genes signature by analyzing single cell RNA-seq data. The study confirmed the prognostic significance of the ferroptosis-related genes in melanoma and developed a novel four-gene prognostic signature (CP, MAP1LC3A, transferrin, and TP53), which may have implications on the prognostic assessment and clinical decision making for melanoma patients (1).

Figure 1. Protein expression of the four prognosis signature genes in normal and melanoma tissue from Human Protein Atlas immunohistochemistry. The gene expression levels of CP, MAP1LC3A and TF are higher in normal tissue and lower in tumor tissue while TP53 had the reverse tendency. (Image from (1),

Signatures in primary and recurrent human cutaneous squamous cell carcinoma

The recurrence of cutaneous squamous cell carcinoma after surgery is associated with the reprogramming of the tumor microenvironment. Using single cell RNA-seq, Li and colleagues (2) examined the dynamic changes in epithelial cells, T cells, myeloid cells, and fibroblasts between primary and recurrent cutaneous squamous cell carcinoma. The study provides insights into the critical mechanisms of cutaneous squamous cell carcinoma progression, which might facilitate the development of a powerful approach for the prevention and treatment of cutaneous squamous cell carcinoma recurrence (2).

Figure 2. Diagram illustrating the reprogramming of tumor microenvironment in cutaneous squamous cell carcinoma progression. Schematic diagram of the tumor microenvironment and cell-cell interactions in primary squamous cell carcinoma (top) and recurrent squamous cell carcinoma (bottom). (Image from (2),

Tumor heterogeneity and immune environment of acral melanoma

Acral melanoma is a type of skin cancer that occurs on fingers, palms, soles, and nail beds, and has a higher incidence in East Asians. Single cell RNA-seq of acral and cutaneous melanoma samples performed by Zhang and colleagues (3) revealed severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells in acral melanoma. Overall, acral melanoma patients are characterized by the severe immunosuppressive state in comparison to cutaneous melanoma patients (3).

Figure 3. Immune cells in acral and cutaneous melanoma. t-SNE plot showing the clusters of immune cells and cell origins by color, according to immune cell types (upper panel), samples (lower left panel), and subtypes (AM/CM, lower right panel). (Image from (3),

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1. Liu, Y., Shou, Y., Zhu, R., et al. Construction and validation of a ferroptosis-related prognostic signature for melanoma based on single-cell RNA s Front. Cell Dev. Biol. 10:818457 (2022). doi: 10.3389/fcell.2022.818457.

2. Li, X., Zhao, S., Bian, X. et al. Signatures of EMT, immunosuppression, and inflammation in primary and recurrent human cutaneous squamous cell carcinoma at single-cell resolution. Theranostics, 12(17), 7532-7549 (2022).

3. Zhang, C., Shen, H., Yang, T. et al. A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma. Nat Commun 13, 7250 (2022).