DPF2 and colon adenocarcinoma: <h4>Background</h4>The crotonylation reader DPF2 has been implicated in tumor progression, but its role in colon adenocarcinoma (COAD), especially in cell-type-specific immune regulation and metabolic reprogramming, remains unclear.<h4>Methods</h4>We conducted an integrative multi-omics study combining genetic association analysis for COAD, public transcriptomic validation data, CRC-context single-cell and spatial transcriptomic datasets used as supportive expression evidence, circulating metabolite profiling, and clinical immunohistochemistry.