From multi-omics to functional validation: the PTMRS stratifies TME and positions PDGFRB in CRC biology

We established a post-translational modification-related risk signature (PTMRS) that robustly stratifies CRC prognosis and links tumor-intrinsic programs with features of the TIME. Higher PTMRS scores, particularly in tumors with <i>PDGFRB</i> enrichment, were associated with a stroma-rich, immune-cold phenotype. Experimental validation highlighted PDGFRβ in colonic fibroblasts as a stromal hub whose activation promotes CRC cell proliferation and migration. These findings suggest that PTMRS may help identify patients who could benefit from combining immunotherapy with therapies targeting PDGFRβ or other PTM-related pathways. Further validation in <i>in vivo</i> models and prospective clinical cohorts is needed.