Serum insulin-like growth factor binding protein 3 as a promising diagnostic and prognostic biomarker in esophagogastric junction adenocarcinoma.

ABSTRACT

BACKGROUND: Esophagogastric junction adenocarcinoma (EJA) lacks serum biomarkers to assist in diagnosis and prognosis. Here, we aimed to evaluate the diagnostic and prognostic value of serum insulin-like growth factor binding protein 3 (IGFBP3) in EJA patients. METHODS: 320 participants were recruited from November 2016 to January 2020, who were randomly divided into a training cohort (112 normal controls and 102 EJA patients including 24 early-stage patients) and a validation cohort (56 normal controls and 50 EJA patients including 12 early-stage patients). We used receiver operating characteristics curve (ROC) to evaluate diagnostic value. The predictive performance of the nomogram was evaluated by the concordance index (C-index). RESULTS: Serum IGFBP3 levels were significantly lower in early-stage EJA or EJA patients than those in controls (P < 0.01). Measurement of serum IGFBP3 demonstrated an area under curve of 0.819, specificity 90.18% and sensitivity 43.14% in training cohort. Similar results were observed in validation cohort (0.804, 87.50%, 42.00%). Importantly, serum IGFBP3 had a satisfactory diagnostic value for early-stage EJA (0.822, 90.18%, 45.83% and 0.811, 84.48%, 50.00% in training and validation cohorts, respectively). Furthermore, survival analysis demonstrated that lower serum IGFBP3 level was related to poor prognosis (P < 0.05). Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic factor (HR = 0.468, P = 0.005). Compared with TNM stage, a nomogram based on serum IGFBP3, tumor size and TNM stage indicated an improved C-index in prognostic prediction (0.625 vs. 0.735, P = 0.001). CONCLUSIONS: We found that serum IGFBP3 was a potential diagnostic and prognostic marker of EJA. Meanwhile, the nomogram might predict the prognosis of EJA more accurately and efficiently.