Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Ductal Adenocarcinoma

Significance Statement

There is no early diagnostic test available for pancreatic ductal adenocarcinoma. In UK study three proteins namely: LYVE1, REG1A and TFF1 were found to be good biomarkers for early detection of pancreatic ductal adenocarcinoma . Patients with pancreatic cancer were found to have increased levels of each of the three proteins when compared to urine samples from healthy patients, the combined analysis of the three proteins gave a robust panel that can detect pancreatic cancer patients with  stages I-II  with > 90% accuracy.

Pancreatic Ductal Adenocarcinoma often diagnosed too late, but if diagnosed earlier such as at stage 2, the survival rate is 20%, and at stage 1, the survival rate for patients can increase up to 60%. Early detection using the three-biomarker test might improve the survival rate of patients with pancreatic ductal adenocarcinoma. It can also be used to screen people at risk (family history of the disease) of developing pancreatic ductal adenocarcinoma.

Identification Three-Biomarker Panel Urine Early Detection Pancreatic Ductal Adenocarcinoma- global medical discovery

Journal Reference

Clin Cancer Res. 2015 Aug 1;21(15):3512-21.

Radon TP1, Massat NJ2, Jones R3, Alrawashdeh W1, Dumartin L1, Ennis D1, Duffy SW2, Kocher HM4, Pereira SP5, Guarner Posthumous L6, Murta-Nascimento C7, Real FX8, Malats N8, Neoptolemos J9, Costello E9, Greenhalf W9, Lemoine NR1,Crnogorac-Jurcevic T10.

[expand title=”Show Affiliations”]

1Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

2Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.

3MS Bioworks, LLC, Ann Arbor, Michigan.

4Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

5Institute for Liver and Digestive Health, University College London, London, United Kingdom.

6Hospital General Universitari Vall Hebron, Barcelona, Spain.

7Hospital del Mar – Parc de Salut Mar, Barcelona, Spain.

8Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.

9The NIHR Liverpool Pancreas Biomedical Research Unit, Liverpool, United Kingdom.

10Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. [email protected].



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 pancreatic ductal adenocarcinoma from healthy individuals.

Proteomes of 18 urine samples from healthy controls, chronic pancreatitis, and patients with pancreatic ductal adenocarcinoma (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.

LYVE-1, REG1A, and TFF1 were selected as candidate biomarkers. When comparing pancreatic ductal adenocarcinoma (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 pancreatic ductal adenocarcinoma 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 pancreatic ductal adenocarcinoma 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 pancreatic ductal adenocarcinoma (n = 17) with 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. Clin Cancer Res; 21(15); 3512-21. ©2015 AACR.

©2015 American Association for Cancer Research.

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New Biomarkers for early detection of pancreatic ductal adenocarcinoma featured on Global Medical Discovery the World’s leading source of medical research news