Methylation profiling revealed gene-specific patterns that both conform to and deviate from classical models: MAP2K1 showed focal hypomethylation yet remained downregulated, suggesting context-dependent feedback regulation; FLNC exhibited gene body hypermethylation correlating with increased transcription; TUBB3 displayed canonical hypomethylation-activation correlation; and ABCA1 demonstrated biphasic methylation with CpG-shore hypermethylation linked to transcriptional repression, underscoring gene-specific epigenetic regulation in cholangiocarcinoma (Figure 5). This evidence concerns the gene TUBB3 and cholangiocarcinoma.