KEY TAKEAWAYS
- The study aimed to investigate the role of CD8+ T cell-related gene markers in creating a prognostic risk model for AM.
- Researchers noticed that the CD8+ T cell gene-based model enhances prognosis and supports personalized immunotherapy in AM.
CD8+ T cells have been recognized as crucial factors in the prognosis of melanoma. However, there is currently a lack of gene markers that accurately describe their characteristics and functions in acral melanoma (AM), which hinders the development of personalized medicine.
Wenwen Wang and the team aimed to assess the utility of CD8+ T cell-related gene markers in developing a prognostic risk model for AM.
They performed an inclusive analysis of immune cell composition in AM using single-cell RNA sequencing (scRNA-seq) data, comprehensively characterizing the immune microenvironment in terms of composition, developmental differentiation, function, and cell communication. A cohort of 95 patients was used to construct and validate a prognostic risk scoring model based on differentially expressed genes (DEGs) related to CD8+ T cells.
This model was developed using the TCGA-SKCM dataset and the Lasso-Cox method. Subsequently, immunofluorescence staining was conducted to validate the expression of four genes (ISG20, CCL4, LPAR6, DDIT3) in AM and healthy skin tissues as included in the prognostic model.
About the results, the scRNA-seq data revealed that memory CD8+ T cells accounted for the highest proportion in the immune microenvironment of AM, reaching 70.5%. Cell-cell communication analysis showed extensive communication relationships among effector CD8+ T cells.
Subsequently, a prognostic scoring model was constructed based on DEGs derived from CD8+ T cell sources, incorporating four CD8+ T cell-related genes into the model. Immunofluorescence results demonstrated that ISG20 and CCL4 were downregulated, while LPAR6 and DDIT3 were upregulated in AM tissues compared to normal skin tissues.
The study concluded that identifying biomarkers based on the expression levels of CD8+ T cell-related genes may be an effective approach for establishing prognostic models in patients with AM. The independently prognostic risk evaluation model constructed provides new insights and theoretical support for immunotherapy in AM.
This study is funded by the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-052, 2023-I2M-3-002, and 2023-I2M-QJ-001) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-061 and 2022-PUMCH-A-022).
Source: https://pubmed.ncbi.nlm.nih.gov/39093712/
Wang W, Liu P, Ma J, et al. (2024). “Establishment of a CD8+ T cells-related prognostic risk model for acral melanoma based on single-cell and bulk RNA sequencing.” Skin Res Technol. 2024 Aug;30(8):e13900. doi: 10.1111/srt.13900. PMID: 39093712; PMCID: PMC11296306.
