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. 2015 Apr 14;112(8):1384-91.
doi: 10.1038/bjc.2015.100. Epub 2015 Mar 17.

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

O M Fisher  1 , A J Levert-Mignon  1 , S J Lord  2 , K K M Lee-Ng  1 , N K Botelho  1 , D Falkenback  3 , M L Thomas  1 , Y V Bobryshev  4 , D C Whiteman  5 , D A Brown  6 , S N Breit  1 , R V Lord  7
Affiliations

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

O M Fisher et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
Boxplot of tissue MIC-1/GDF15 mRNA expression analysis by pathology diagnosis. Raw relative mRNA expression values are presented. Differences in relative gene expression values were calculated using Student's t-test following log2 transformation. Bold values indicates that these are statistically significant. Dot indicates outlier as is convention for presenting boxplot data.
Figure 2
Figure 2
Boxplots of MIC-1/GDF15 plasma levels by pathology diagnosis and corresponding receiver operator characteristic (ROC) curves for performance analysis of tissue MIC-1/GDF15 plasma levels to discriminate patient groups. (A and B) Show the analysis of the whole study cohort, whereas (C and D) depict the findings in the non-obese, non-underweight (as categorised by the WHO) patient population. Differences in plasma values were calculated using Student's t-test following log2 transformation. Data are presented untransformed as pg ml−1. Bold values indicates that these are statistically significant. Dot indicates outlier as is convention for presenting boxplot data. **P<0.01; ***P<0.001.
Figure 3
Figure 3
Survival of OAC patients stratified by MIC-1/GDF15 plasma levels ⩾1140 pg ml−1 (as determined by ROC curve analysis).
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