PT  - JOURNAL ARTICLE
AU  - Radon, Tomasz P.
AU  - Massat, Nathalie J.
AU  - Jones, Richard
AU  - Alrawashdeh, Wasfi
AU  - Dumartin, Laurent
AU  - Ennis, Darren
AU  - Duffy, Stephen W.
AU  - Kocher, Hemant M.
AU  - Pereira, Stephen P.
AU  - Guarner (posthumous), Luisa
AU  - Murta-Nascimento, Cristiane
AU  - Real, Francisco X.
AU  - Malats, Núria
AU  - Neoptolemos, John
AU  - Costello, Eithne
AU  - Greenhalf, William
AU  - Lemoine, Nick R.
AU  - Crnogorac-Jurcevic, Tatjana
TI  - Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma
AID  - 10.1158/1078-0432.CCR-14-2467
DP  - 2015 Aug 01
TA  - Clinical Cancer Research
PG  - 3512--3521
VI  - 21
IP  - 15
4099  - http://clincancerres.aacrjournals.org/content/21/15/3512.short
4100  - http://clincancerres.aacrjournals.org/content/21/15/3512.full
SO  - Clin Cancer Res2015 Aug 01; 21
AB  - Purpose: Noninvasive 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.Experimental design: Proteomes of 18 urine samples from healthy controls, chronic pancreatitis, and patients with PDAC (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated with ELISA assays using multiple logistic regression applied to a training dataset in a multicenter cohort comprising 488 urine samples.Results: LYVE-1, REG1A, and TFF1 were selected as candidate biomarkers. When comparing PDAC (n = 192) with healthy (n = 87) urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the panel were 0.89 [95% confidence interval (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) with healthy urine specimens, 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) with healthy urine.Conclusions: We have established a novel, three-protein biomarker panel that is able to detect patients with early-stage pancreatic cancer in urine specimens. Clin Cancer Res; 21(15); 3512–21. ©2015 AACR.