Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.
Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-14-2467
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发表时间：
2015-08-01
期刊：
影响因子：
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通讯作者：
Crnogorac-Jurcevic T
中科院分区：
文献类型：
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作者：
Radon TP;Massat NJ;Jones R;Alrawashdeh W;Dumartin L;Ennis D;Duffy SW;Kocher HM;Pereira SP;Guarner posthumous L;Murta-Nascimento C;Real FX;Malats N;Neoptolemos J;Costello E;Greenhalf W;Lemoine NR;Crnogorac-Jurcevic T
目前尚无非侵入性生物标志物可用于胰腺导管腺癌(PDAC)的早期检测。在这里，我们的目标是识别一组能够区分早期PDAC患者和健康人(H)的尿蛋白。用GeLC/MS/MS分析了18例正常人、慢性胰腺炎和PDAC患者(6例/组)的尿液蛋白质组。随后，在包括488个尿样的多中心队列中，使用应用于训练数据集的多重Logistic回归的ELISA法来验证所选择的生物标记物。LYVE-1、REG1A和TFF1被选为候选生物标志物。当比较PDAC(n=192)和健康(n=87)尿时，面板的受试者工作特征曲线(AUC)下的面积在训练(70%的数据)中为0.89(95%可信区间0.84-0.94)，在验证(30%的数据)数据集中为0.92(95%可信区间0.86-0.98)。当比较PDAC阶段I-II期(n=71)和健康尿液时，小组在训练和验证数据集中分别获得0.90(95%可信区间0.84-0.96)和0.93(95%可信区间0.84-1.00)的AUC值。在PDACI-II期和血浆CA19.9配对的健康样本中，面板获得的AUC0.97(95%CI0.94-0.99)高于CA19.9(AUC0.88，95%CI0.81-0.95，P=0.005)。加入CA19.9使AUC从0.97(95%可信区间0.94~0.99)增加到0.99(95%可信区间0.97~1.00，p=0.04)，但并未改善I-IIA PDAC(n=17)阶段与健康尿样的比较。我们已经建立了一种新的三蛋白生物标记物小组，能够从尿样中检测早期胰腺癌患者。
Non-invasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available. Here, we aimed to identify a set of urine proteins able to distinguish patients with early stage PDAC from healthy individuals (H). Proteomes of 18 urine samples from healthy controls, chronic pancreatitis and PDAC patients (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated using ELISA assays using multiple logistic regression applied to a training dataset in a multicentre cohort comprising 488 urine samples. LYVE-1, REG1A and TFF1 were selected as candidate biomarkers. When comparing PDAC (n=192) to healthy (n=87) urines, the resulting areas under the receiver operating characteristic curves (AUCs) of the panel were 0.89 (95%CI 0.84-0.94) in the training (70% of the data), and 0.92 (95%CI 0.86-0.98) in the validation (30% of the data) datasets. When comparing PDAC stage I-II (n=71) to healthy urines, the panel achieved AUCs of 0.90 (95%CI 0.84-0.96) and 0.93 (95%CI 0.84-1.00) in the training and validation datasets, respectively. In PDAC stage I-II and healthy samples with matching plasma CA19.9 the panel achieved a higher AUC of 0.97 (95%CI 0.94-0.99) than CA19.9 (AUC=0.88, 95%CI 0.81-0.95, p=0.005). Adding plasma CA19.9 to the panel increased the AUC from 0.97 (95%CI 0.94-0.99) to 0.99 (95%CI 0.97-1.00, p=0.04) but did not improve the comparison of stage I-IIA PDAC (n=17) to healthy urine. We have established a novel, three-protein biomarker panel that is able to detect patients with early stage pancreatic cancer in urine specimens.