Serum and tissue IGFBP2 as a prognostic biomarker in gastric adenocarcinoma: A multi-cohort clinical validation study

BACKGROUND: At present, the relevance of insulin-like growth factors in the progression of gastric cancer (GC) remains elusive. We conducted a cohort study to assess the influence of the IGF proteins on GC. METHODS: We investigated the serum and tissue expression of IGF proteins in patients with GC to determine their biomarker potential. In Cohort 1, the serum levels of IGF1,2, and IGFBP1-3 were measured for survival analysis (N = 142). IGF1,2, IGF-IR,IIR, and IGFBP1-3 in cancer tissues was assessed via immunohistochemistry (N = 28). In Cohort 2 (N = 255), serum IGFBP2 was measured 115 patients diagnosed with gastritis as a control group. In prognostic Cohort 3 (N = 397), IGFBP2 expression was quantitatively assessed in GC tissues. RESULTS: Higher serum IGFBP2 in Cohorts 1 and 2 was associated with worse overall survival (Cohort 1, p < 0.0001; Cohort 2, p < 0.00001). In Cohort 1, IGFBP2 exhibited the highest success staining rate among IGF proteins in GC tissue (92.8%, 26/28; p = 0.006). Cox regression analysis confirmed that higher serum IGFBP2 predicted a worse prognosis (HR: 1.90; p = 0.0011). The serum IGFBP2 levels in GC patients were higher than in the gastritis group (p = 0.0001). Cox regression analysis in Cohort 3 suggested that score 2 and score 1 IGFBP2 expression were independent predictors of poor prognosis (HR: 1.74 for Score 2, p = 0.0079; HR: 1.49 for Score 1, p = 0.039). CONCLUSIONS: IGFBP2, but not other IGF proteins, are associated with GC prognosis.