Liu Yurong, Liu Jianlan, Jiang Keyu, Cheng Xiaolong, Di Sitong, Tang Jian, Luo Binlin
The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Iran J Allergy Asthma Immunol. 2025 Mar 10;24(2):237-253. doi: 10.18502/ijaai.v24i2.18150.
Regulatory T cells (Tregs) are central to establishing an immunosuppressive tumor microenvironment (TME), which promotes cancer progression and influences therapeutic outcomes. However, the prognostic significance of Treg-related genes (TRGs) in predicting immunotherapy response in melanoma remains insufficiently characterized. This study seeks to elucidate the role of TRGs in the antitumor immune response of melanoma. The ordinary transcriptome and single-cell RNA sequencing (scRNA-seq) data were obtained from the gene expression omnibus and the cancer genome atlas databases. A multi-tiered quality control process was applied to scRNA-seq data, followed by cell annotation, cell-cell communication, and enrichment analysis to investigate Treg function in the melanoma microenvironment. Weighted gene coexpression network analysis (WGCNA) was employed to identify modules associated with Treg infiltration. Key prognostic genes were identified using univariate Cox regression analysis and integrated into a prognostic model through least absolute shrinkage and selection operator and stepwise regression methods. The analysis revealed a Treg-related gene signature (TRGS) comprising CHD3, FOSB, SEMA4D, PSME1, FYN, PRKACB, and ARID5A. Higher TRGS-based risk scores were significantly associated with worse prognoses, immune cell infiltration, and stromal scores. TRGS was identified as an independent prognostic indicator for melanoma, offering novel insights into the role of Tregs in modulating the TME. This study highlights the potential clinical utility of TRGs in melanoma diagnostics and personalized immunotherapy, providing a robust foundation for future therapeutic strategies.
调节性T细胞（Tregs）对于建立免疫抑制性肿瘤微环境（TME）至关重要，该微环境促进癌症进展并影响治疗结果。然而，Treg相关基因（TRGs）在预测黑色素瘤免疫治疗反应中的预后意义仍未得到充分表征。本研究旨在阐明TRGs在黑色素瘤抗肿瘤免疫反应中的作用。普通转录组和单细胞RNA测序（scRNA-seq）数据来自基因表达综合数据库和癌症基因组图谱数据库。对scRNA-seq数据应用了多层质量控制过程，随后进行细胞注释、细胞间通讯和富集分析，以研究黑色素瘤微环境中的Treg功能。采用加权基因共表达网络分析（WGCNA）来识别与Treg浸润相关的模块。使用单变量Cox回归分析确定关键预后基因，并通过最小绝对收缩和选择算子以及逐步回归方法将其整合到预后模型中。分析揭示了一个由CHD3、FOSB、SEMA4D、PSME1、FYN、PRKACB和ARID5A组成的Treg相关基因特征（TRGS）。基于TRGS的较高风险评分与较差的预后、免疫细胞浸润和基质评分显著相关。TRGS被确定为黑色素瘤的独立预后指标，为Tregs在调节TME中的作用提供了新的见解。本研究强调了TRGs在黑色素瘤诊断和个性化免疫治疗中的潜在临床应用价值，为未来的治疗策略提供了坚实的基础。
