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

Figure 1 Intercellular adhesion molecule 2 expression correlates with 5-fluorouracil resistance and predicts neoadjuvant chemotherapy response in advanced gastric cancer patients. A and B: Correlation between 5-fluorouracil (5-FU) half-maximal inhibitory concentration values and intercellular adhesion molecule 2 (ICAM2) protein expression in the gastric cancer (GC) cell lines; C: Time-dependent changes in ICAM2 protein levels following 5-FU treatment; D and E: Immunohistochemistry analysis of ICAM2 expression in chemo-sensitive and chemo-resistant advanced GC (AGC) patients before and after neoadjuvant chemotherapy (NACT); F: ROC curve based on pre-NACT tumor tissue ICAM2 levels to differentiate between chemo-sensitive and chemo-resistant patients; G: Enzyme-linked immunosorbent assay (ELISA) analysis of serum ICAM2 levels in the training cohort, comparing chemo-sensitive and chemo-resistant patients before and after NACT; H: Receiver-operating characteristic (ROC) curve based on pre-NACT serum ICAM2 concentrations to predict NACT response; I and J: Kaplan-Meier survival curves showing overall survival and disease-free survival for AGC patients with low or high pre-NACT serum ICAM2 levels; K: ELISA analysis of serum ICAM2 levels in the validation cohort, comparing chemo-sensitive and chemo-resistant patients prior to NACT; L: ROC curve analysis using pre-NACT serum ICAM2 levels to distinguish between chemo-sensitive and chemo-resistant patients. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ^dP < 0.0001. 5-FU: 5-fluorouracil; IC₅₀: Half-maximal inhibitory concentration; ICAM2: Intercellular adhesion molecule 2; NACT: Neoadjuvant chemotherapy; ROC: Receiver-operating characteristic; AUC: Area under the curve; ELISA: Enzyme-linked immunosorbent assay; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.