Genome-wide DNA methylation landscapes in gallbladder carcinoma: revealing shared and distinct epigenetic signatures...

Gallbladder cancer is an aggressive malignancy with poor survival rates, there are biologically distinct subtypes, yet genome-wide epigenetic differences remain poorly understood. This study was designed as an exploratory investigation of subtype-specific DNA methylation patterns.

The study included sixteen gallbladder tissue sample (adenocarcinoma, n = 6; ICPN with invasion, n = 6; controls, n = 4). Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC (850K) array. Differential methylation was assessed using Δβ ≥ 0.2 and FDR < 0.05, with emphasis on effect sizes. Chromosomal distribution, CpG island annotation, Gene Ontology enrichment, protein-protein interaction networks, and promoter-specific methylation patterns were examined.

GBC demonstrated predominant global hypomethylation, with adenocarcinoma showing marked promoter hypomethylation (79.2%), compared with ICPN (54.7%). Adenocarcinoma exhibited enrichment of transcriptional and proliferative pathways whereas ICPN showed stress-response, autophagy, and apoptotic pathway enrichment. A set of 543 consensus genes displayed recurrent methylation changes across all comparisons, suggesting shared epigenetic remodeling duringndisease progression.

This exploratory study identifies distinct and shared epigenetic signatures across gallbladder carcinoma subtypes, highlighting subtype-specific promoter remodeling. These findings provide a foundation for future large-scale validation studies integrating methylation, transcriptomic, and clinical outcome.