Expression level of 887 DEGs in GSE46517.

Background
Metastatic melanoma is a challenging clinical condition with poor prognosis. Recent research has highlighted the role of antibody-dependent cellular phagocytosis (ADCP) in tumor immunity, suggesting prognostic implications for ADCP-related genes (ARGs). This study develops a prognostic model for metastatic melanoma using ARGs to enhance clinical decision-making and therapeutic strategies.
Methods
Prognostic ARGs were identified from the GSE46517 and GSE7553 datasets. A prognostic model was constructed using LASSO-Cox regression and validated across multiple cohorts, including TCGA and GEO datasets. A nomogram was developed to assess survival outcomes in metastatic melanoma patients. Functional assays, including siRNA knockdown of DOCK10 in A375 cells, were conducted to validate the role of DOCK10 in melanoma progression.
Results
A prognostic model based on six ARGs—NDRG1, HRAS, KPNA2, ICAM1, DOCK10, and CDC20—was developed. Patients were stratified into high- and low-risk groups based on risk scores, with high-risk patients showing poorer overall survival (OS) in both validation cohorts. The model was validated as an independent prognostic factor. Gene set enrichment analysis (GSEA) indicated that the low-risk group was enriched in immune-related pathways. High-risk patients exhibited higher genomic instability, which was associated with poorer prognosis. Knockdown of DOCK10 in A375 cells significantly reduced proliferation, migration, and invasion, confirming its role in melanoma progression.
Conclusion
The model also demonstrated associations with immune cell infiltration and drug sensitivity, highlighting its potential utility in optimizing immunotherapy and chemotherapy strategies. This study developed a novel ARG-based prognostic model that aids in survival prediction and therapeutic decision-making for metastatic melanoma patients. DOCK10 was identified as a potential therapeutic target in melanoma metastasis.

背景
转移性黑色素瘤是一种极具挑战性的临床病症，预后不良。近期研究揭示了抗体依赖性细胞吞噬作用（antibody-dependent cellular phagocytosis, ADCP）在肿瘤免疫中的作用，提示ADCP相关基因（ADCP-related genes, ARGs）具有预后价值。本研究基于ADCP相关基因构建转移性黑色素瘤的预后模型，以期优化临床决策与治疗策略。
方法
从GSE46517与GSE7553数据集中共筛选得到预后相关ADCP相关基因。采用最小绝对收缩和选择算子-考克斯（LASSO-Cox）回归构建预后模型，并在包括癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因表达综合数据库（Gene Expression Omnibus, GEO）数据集在内的多队列中进行验证。构建列线图以评估转移性黑色素瘤患者的生存结局。通过功能实验验证DOCK10在黑色素瘤进展中的作用，具体为在A375细胞中利用小干扰RNA（small interfering RNA, siRNA）敲低DOCK10的表达。
结果
本研究构建了基于6个ADCP相关基因（NDRG1、HRAS、KPNA2、ICAM1、DOCK10及CDC20）的预后模型。根据风险评分将患者分为高风险组与低风险组，在两个验证队列中，高风险组患者的总生存期（overall survival, OS）均更短。该模型被证实为独立预后因素。基因集富集分析（gene set enrichment analysis, GSEA）结果显示，低风险组显著富集于免疫相关通路。高风险组患者的基因组不稳定性更高，且这与不良预后相关。在A375细胞中敲低DOCK10的表达可显著抑制细胞增殖、迁移与侵袭能力，证实了其在黑色素瘤进展中的作用。
结论
该模型还与免疫细胞浸润及药物敏感性存在关联，提示其在优化免疫治疗与化疗策略方面具有应用潜力。本研究构建了一种基于ADCP相关基因的新型预后模型，可辅助转移性黑色素瘤患者的生存预测与治疗决策。同时鉴定出DOCK10可作为黑色素瘤转移的潜在治疗靶点。