MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma

Background:Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC.Methods:One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC.Results:Median tissue expression of MIC-1/GDF15 mRNA was ≥25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (≥1140 pg ml-1) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047).Conclusions:Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.