Integrative analysis of adiponectin-related genes reveals immune subtypes and prognostic significance in melanoma.

AIMSThis study aimed to explore the prognostic and immune-related associations of adiponectin-related genes in melanoma.

METHODSSingle nucleotide polymorphism (SNP) and transcriptomic data from the Integrative Epidemiology Unit Open Genome-Wide Association Study database (IEU openGWAS) and The Cancer Genome Atlas Skin Cutaneous Melanoma cohort (TCGA-SKCM) were integrated to identify adiponectin-related genes. Consensus clustering defined molecular subtypes. Differentially expressed genes (DEGs) were analyzed using functional enrichment, protein-protein interaction (PPI), and immune infiltration (CIBERSORT). In vitro assays assessed transcriptional changes following endogenous albumin (ALB) modulation in melanoma cells.

RESULTSFive adiponectin-associated SNPs were linked to melanoma prognosis. Four molecular subtypes with distinct survival outcomes were identified, with ALB-high Cluster 3 showing the poorest prognosis. A total of 702 DEGs were enriched in immune-related pathways, including IL-17 signaling and antigen presentation. ALB was identified as a PPI hub and positively correlated with memory B cells (R = 0.34, P = 0.012). In vitro, ALB overexpression was associated with increased mRNA levels of IL-6, TNF-α, TGF-β, IL-17A, and RORγt.

CONCLUSIONTumor-associated ALB expression is associated with adverse prognosis and immune-related transcriptional features in melanoma, suggesting its potential as a prognostic biomarker and marker of transcriptomic heterogeneity.