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.

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.

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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].

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Abstract
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 pancreatic ductal adenocarcinoma from healthy individuals.

EXPERIMENTAL DESIGN:
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.

RESULTS:
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.

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.

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