Page 14 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Single-cell RNA-seq in malignant skin tumors

Table 1. Key studies associated with the use of single‑cell RNA sequencing in basal cell carcinoma
Cancer Cell Properties Authors Key findings
type origin
BCC Basal cells Slow growth and low malignant Guerrero-Juarez et al. 20 HSP genes, especially HSP70 family members, as potential new
regulators of BCC tumor growth and HH pathway, may provide a new
therapeutic target for the treatment of BCC.
Haensel et al. 21 Identified a subpopulation of TREM2 macrophages, promoting tumor
+
epithelial cell proliferation through the JAK-STAT3 signaling pathway.
Huang et al. 23 Identified MDK expressed in malignant cells, serves as an
independent predictor for the depth of infiltration in infiltrative BCC.
Pich-Bavastro et al. 24 Integrated ST and scRNA-seq, identified CAFs and macrophages,
contributing to CD8 T-cell exhaustion and immune suppression, as
well as resistance to ICB.
Yost et al. 25 Conducted paired scRNA-seq and TCR-seq, revealing a clonal
replacement phenomenon of tumor-specific T-cells after PD-1
blockade therapy.
Abbreviations: BCC: Basal cell carcinoma; CAF: Cancer-associated fibroblast; HH: Hedgehog; HSP: Heat shock protein; ICB: Immune checkpoint
blockade; MDK: Midkine; scRNA-seq: Single-cell RNA sequencing; ST: Spatial Transcriptomics; TCR-seq: T-cell receptor sequencing.

chromosomal copy number variations (CNVs) in SCCIS with group 3. Single-cell data revealed convergence of stem
suggested increased invasiveness and potential progression cell states across different cell types. Group 3, enriched in
to invasive cSCC. In addition, Li et al. identified that oxidative stress and lineage plasticity, was found in the
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MDK could induce various cell-cell interactions in cSCC lower spike cell subset, while group 1, linked to cell cycle
at different stages through scRNA-seq analysis. In primary activation and genomic instability, was localized to the
cSCC, MDK was highly expressed in fibroblasts, promoting upper spike subset. The study highlights two mutually
proliferation and inhibiting tumor cell migration. exclusive stem cell states in cSCC progression: high
Conversely, in recurrent cSCC, elevated MDK expression proliferation and high plasticity. In vitro experiments
in TSKs promoted their proliferation and metastasis. emphasized the importance of transitioning between
Wang et al. classified T-cell populations into seven these states for effective cSCC therapy. Unlike previous
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subgroups in BCC and cSCC, including CD8 activation, studies, Fontana et al. validated that traditional protein-
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CD8 exhaustion, memory CD8, naïve T, T follicular based specific CAF markers struggle to distinguish normal
helper, Th17, and Treg cells. The study reported higher fibroblasts (NF) from CAF in clinical samples of both
expression of cytolytic effector genes GZMA and RPF1 BCC and cSCC. It was found that in comparison to NF,
in T-cells within cSCC compared to BCC, with overall the proportion of mitochondrial DNA (mtDNA) common
cytolytic activity also elevated in cSCC. Schütz et al. deletion content significantly decreases in CAFs from both
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revealed immunoregulatory and matrix-remodeling CAF BCC and cSCC, accompanied by upregulation of genes
subtypes, potentially originating from pro-inflammatory involved in mtDNA maintenance. The study proposed
and mesenchymal fibroblasts. These CAF subtypes are mtDNA common deletion heterogeneity and expression of
notably scarce in AK and interact with distinct cell mtDNA-encoded genes as potential biomarkers, offering
types to establish a pro-tumorigenic microenvironment. novel insights for BCC and cSCC research (Table 2).
Yan et al. conducted single-cell transcriptome sequencing
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on primary UV-induced cSCCs alongside matched 5. Advancements in single-cell RNA-seq in
adjacent skin samples, revealing notable differences in gene CM research
expression and chromosomal CNVs between cSCC cells
and normal keratinocytes. Particularly, the study identified 5.1. The main characteristics and treatment options
significantly upregulated genes S100A9 and FABP5, for CM
which are implicated in promoting cell proliferation and CM is a malignant skin tumor that primarily originates
migration, potentially providing new targets for future from melanocytes, which are derived from the neural crest
therapeutic interventions in cSCC. A recent study on stem and responsible for producing the skin pigment melanin.
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cell status in cSCC identified a stem cell network evolving Although CM represents only 4% of all skin cancers, it
through cancer stages using bulk RNA-seq. Three gene accounts for 75% of skin cancer-related deaths. According
clusters were found, with group 1 negatively correlating to GLOBOCAN estimates for 2022, there were 331,647
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Volume 9 Issue 1 (2025) 6 doi: 10.36922/ejmo.5809