BACKGROUND Early detection would improve upper gastrointestinal cancer prognosis. We aimed to identify serum protein biomarker for the detection of early-stage upper gastrointestinal cancer. METHODS We performed a three-tiered study including 2028 participants from three medical centres. First, we applied two different antibody arrays to screen candidate serum proteins that increased in 20 patients with oesophageal squamous cell carcinoma (ESCC) compared with 20 normal controls. We then evaluated the selected protein by enzyme-linked immunosorbent assay in 1064 participants including 731 upper gastrointestinal cancer patients (287 ESCCs, 237 oesophagogastric junction adenocarcinomas (EJAs), and 207 stomach cancers) and 333 normal controls. The diagnostic value of the selected protein was finally validated in two independent cohorts of ESCC patients and controls (n=472 and 452, respectively). The receiver operating characteristic was used to calculate diagnostic accuracy. FINDINGS Serum insulin-like growth factor binding protein-1 (IGFBP-1) identified in both antibody arrays showed significantly elevated levels in upper gastrointestinal cancers, compared with normal controls. Serum IGFBP-1 provided high diagnostic accuracy of early-stage ESCC, EJA, stomach and cancer (areas under the curve: 0·898, 0·936 and 0·864, respectively). This protein maintained diagnostic performance for early-stage ESCC in independent cohorts 1 and 2 (0·849 and 0·911, respectively). Additionally, serum levels of IGFBP-1 dropped significantly after surgical resection of primary tumours, compared with the corresponding pre-operative ESCC samples (p < 0·05). INTERPRETATION Serum IGFBP-1 represents a promising diagnostic biomarker to detect early-stage upper gastrointestinal cancer.

中文翻译：

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血清IGFBP-1可作为诊断早期上消化道肿瘤的潜在生物标志物。

背景技术及早发现将改善上消化道癌的预后。我们旨在鉴定血清蛋白生物标志物，以检测早期上消化道癌。方法我们进行了一项三层研究，包括来自三个医疗中心的2028名参与者。首先，我们应用了两种不同的抗体阵列来筛选与20名正常对照相比在20例食管鳞状细胞癌（ESCC）患者中增加的候选血清蛋白。然后，我们通过酶联免疫吸附测定法对1064名参与者（包括731名上消化道癌症患者（287名ESCC，237名食管胃交界性腺癌（EJAs）和207名胃癌）和333名正常对照）进行了评估，评估了所选的蛋白质。最后，在两个独立的ESCC患者和对照队列中分别验证了所选蛋白的诊断价值（分别为n = 472和452）。接收器的工作特性用于计算诊断准确性。结果在两个抗体阵列中鉴定出的血清胰岛素样生长因子结合蛋白-1（IGFBP-1）与正常对照组相比在上消化道癌中显示出明显升高的水平。血清IGFBP-1对早期ESCC，EJA，胃癌和癌症（曲线下面积分别为0·898、0·936和0·864）具有较高的诊断准确性。该蛋白在独立队列1和2（分别为0·849和0·911）中保持了早期ESCC的诊断性能。此外，手术切除原发肿瘤后，IGFBP-1的血清水平显着下降，与相应的术前ESCC样本进行比较（p <0·05）。血清IGFBP-1代表了一种有前途的诊断性生物标志物，可检测早期的上消化道癌。