Fisher O M, Levert-Mignon A J, Lord S J, Lee-Ng K K M, Botelho N K, Falkenback D, Thomas M L, Bobryshev Y V, Whiteman D C, Brown D A, Breit S N, Lord R V
St Vincent's Centre for Applied Medical Research and University of New South Wales, Sydney, NSW 2010 Australia.
1] St Vincent's Centre for Applied Medical Research and University of New South Wales, Sydney, NSW 2010 Australia [2] NHMRC Clinical Trials Centre University of Sydney, Sydney, NSW 2050, Australia [3] Department of Epidemiology and Medical Statistics, School of Medicine, University of Notre Dame, Sydney, NSW 2010 Australia.
Br J Cancer. 2015 Apr 14;112(8):1384-91. doi: 10.1038/bjc.2015.100. Epub 2015 Mar 17.
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.
One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC.
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).
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.
需要生物标志物来改善目前对巴雷特食管（BO）和食管腺癌（OAC）患者的诊断和监测策略。巨噬细胞抑制细胞因子1/生长分化因子15（MIC-1/GDF15）的组织和血浆水平已被证明可预测其他癌症类型的疾病进展，因此对BO/OAC进行了评估。
研究了138例患者：45例正常食管（NE）、37例BO、16例低级别异型增生（LGD）的BO和40例OAC。
与NE相比，BO和LGD中MIC-1/GDF15 mRNA的中位组织表达高≥25倍（P<0.001）；OAC与BO相比高2倍（P=0.039）；OAC与NE相比高47倍（P<0.001）。相对MIC-1/GDF15组织表达>720可区分OAC或LGD与NE的存在，敏感性为94%，特异性为71%（ROC曲线下面积0.86，95%可信区间0.73-0.96；P<0.001）。OAC患者的巨噬细胞抑制细胞因子1/生长分化因子15血浆值也高于NE（P<0.001）或BO（P=0.015）。高MIC-1/GDF15血浆水平（≥1140 pg/ml）是OAC患者生存不良的独立预测因素（风险比3.87，95%可信区间1.01-14.75；P=0.047）。
BO、LGD和OAC患者的MIC-1/GDF15血浆和组织水平显著升高。血浆MIC-1/GDF15可能在巴雷特病的诊断和监测中具有价值。
