Page 15 - EJMO-9-1

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

Table 2. Key studies associated with the use of single‑cell RNA sequencing in cutaneous squamous cell carcinoma
Cancer Cell origin Properties Authors Key findings
type
cSCC Epidermis or appendage Low rates of metastasis Ji et al. 33 Identified a TSK subgroup in cSCC, as a hub for intercellular
keratinocytes and mortality communication.
Zou et al. 34 Highlighted the progression of normal skin, AK to cSCC, basal cell
subpopulations with high expression of stem cell-related markers, and
higher levels of CNV in cSCC.
Li et al. 35 MDK could induce various cell-cell interactions in cSCC at different stages.
Schütz et al. 37 Revealed immunoregulatory and matrix-remodeling CAF subtypes,
potentially originating from pro-inflammatory and mesenchymal
fibroblasts, respectively.
Abbreviations: AK: Actinic keratosis; CAF: Cancer-associated fibroblast; CNV: Copy number variant; cSCC: Cutaneous squamous cell carcinoma;
MDK: Midkine; TSK: Tumor-specific keratinocyte.

new cases of CM and 58,645 related deaths globally. The Building on the work of Tirosh et al., Li et al. further
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incidence of CM varies significantly across countries and identified significant differences in cell composition,
regions, attributed to differences in racial skin phenotypes CNVs, and biological functions among melanoma samples,
and sun exposure. Individuals with prolonged exposure to suggesting a potential relationship between different
sunlight, especially those prone to sunburn, are at higher cellular components and the tumor state. The cholesterol
risk of developing melanoma. Other factors associated metabolism pathway has been identified as a crucial factor
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with CM occurrence include alcohol consumption, while in the malignant phenotypes of melanoma. Apolipoprotein
smoking does not show a significant causal relationship C-II (APOC2) regulates this pathway, indicating that low
with CM development (OR: 0.85; 95% CI: 0.54 – 1.35; levels of APOC2 may inhibit melanoma migration. In
P = 0.50). 44,45 In addition, genetic factors also play a addition, results from CancerSEA showed a significant
critical role in the occurrence and development of CM, 46- correlation between APOC2 expression and melanoma
48 including the number, size, and type of congenital and metastasis (correlation strength > 0.3, P < 0.01), suggesting
acquired melanocytic nevi, 49,50 genetic susceptibility, 51-53 that variations in APOC2 expression levels may contribute
and family history. 53,54 At present, treatment options for CM to melanoma heterogeneity. 64,65 In a comprehensive
encompass early surgical excision, lymph node examination, analysis of 7,186 cells from 31 CM patients, Kang et al.
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immunotherapy, and targeted therapy. However, despite uncovered heterogeneity among melanocytes within and
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these advancements, clinical management of CM presents between tumors. A non-negative matrix factorization was
several challenges. 56-59 CM may initially manifest as small employed to identify six common patterns of intratumoral
asymptomatic lesions, leading to delayed diagnoses in some heterogeneity, some of which were associated with poor
patients. Its high invasiveness and metastatic potential prognosis or promoted resistance to immunotherapy.
pose significant hurdles to treatment, particularly once
metastasis occurs, complicating therapeutic interventions The presence and activity of tumor-infiltrating
and worsening prognosis. In addition, some melanomas lymphocytes are crucial for the development and
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exhibit immune escape characteristics or resistance to prognosis of melanoma patients. Deng et al. identified
treatment, further adding to the complexity and challenges seven CD8 T-cell subtypes from 59 melanoma samples,
of treatment. Single-cell research plays a pivotal role in revealing heterogeneity in key genes, pathway activities,
melanoma research by offering deeper insights into tumor and ligand-receptor interactions among different subtypes.
heterogeneity, developmental processes, and potential Trajectory analysis found that the exhaustion-associated
therapeutic avenues. subgroup 2 represented the terminal state of CD8 T-cell
differentiation, leading to poor prognosis. High expression
5.2. Single-cell analysis of tumor heterogeneity in of PMEL, TYRP1, and EDNRB genes in this subgroup
CM suggests potential novel therapeutic targets. Yan et al.
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Research indicates that CM is a highly heterogeneous employed single-cell transcriptomics to analyze gene
tumor, with diversity in cell composition and interactions expression patterns of individual T-cells in melanoma
among different cell types playing a crucial role in tissues, discovering clusters of exhausted cells enriched
malignant progression and treatment resistance. Single- with tumor-reactive T-cells. A set of tumor-reactive
cell technologies excel in revealing this heterogeneity. 60-62 T-cell signature genes was also developed and validated

Volume 9 Issue 1 (2025) 7 doi: 10.36922/ejmo.5809