Urine Biomarker Panel Detects Early Pancreatic Cancer

Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary, University of London London UKMedicalResearch.com Interview with:
Tatjana Crnogorac-Jurcevic MD PhD
Reader Centre for Molecular Oncology
Barts Cancer Institute, Queen Mary
University of London
London UK 

Medical Research: What is the background for this study? What are the main findings?
Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%.

In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients.

Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison.

Medical Research: What should clinicians and patients take away from your report?

Dr. Crnogorac-Jurcevic: We have established a novel, three-protein biomarker panel that is able to detect patients with early-stage Pancreatic adenocarcinoma through analysis of urine specimens. This panel could, after further validation, offer a possibility of completely non-invasive and inexpensive screening of individuals at high risk of developing this malignancy (e.g. members of pancreatic cancer families and several hereditary syndromes that show increased incidence of this cancer).

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Crnogorac-Jurcevic: We now need to validate the diagnostic performance of our biomarker panel directly on urine samples collected from high-risk individuals. In addition, through analysis of longitudinally collected urine specimens, we would like to establish how early in the latency period our panel can detect pancreatic adenocarcinoma.

We hope that with ease of sampling and repeated testing our urinary panel will translate to long sought-after non-invasive diagnostic tool for detection of pancreatic adenocarcinoma in early stages, when patients can still be cured by surgical resection.

Citation:

Tomasz P. Radon, Nathalie J. Massat, Richard Jones, Wasfi Alrawashdeh, Laurent Dumartin, Darren Ennis, Stephen W. Duffy, Hemant M. Kocher, Stephen P. Pereira, Luisa Guarner (posthumous), Cristiane Murta-Nascimento, Francisco X. Real, Núria Malats, John Neoptolemos, Eithne Costello, William Greenhalf, Nick R. Lemoine, and Tatjana Crnogorac-Jurcevic. Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma. Clinical Cancer Research, August 2015 DOI: 10.1158/1078-0432.CCR-14-2467

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Tatjana Crnogorac-Jurcevic MD PhD (2015). Urine Biomarker Panel Detects Early Pancreatic Cancer