Exploring the impact of antibody-dependent cellular phagocytosis-related genes on the prognosis of metastatic melanoma.

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.