ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer

Figure 3 Pleiotrophin mediates intercellular adhesion molecule 2-driven chemoresistance to 5-fluorouracil in gastric cancer. A: Gene Ontology enrichment analysis of differentially expressed genes (DEGs); B: Heatmap showing expression patterns of DEGs between control and intercellular adhesion molecule 2 (ICAM2)-overexpressing cells (red = upregulated, blue = downregulated, based on z-score of normalized expression); C: Real-time PCR validation of DEG expression; D: Changes in pleiotrophin (PTN) protein expression following ICAM2 overexpression or knockdown; E: PTN promoter activity assessed in the indicated cell models using a dual-luciferase reporter assay; F-I: Cytotoxicity, colony formation, flow cytometry, and apoptosis-related protein assays evaluating the reversal of ICAM2-mediated 5-fluorouracil resistance by PTN overexpression or silencing. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ^dP < 0.0001. PTN: Pleiotrophin; 5-FU: 5-fluorouracil; IC₅₀: Half-maximal inhibitory concentration; ICAM2: Intercellular adhesion molecule 2; GO: Gene Ontology.