Robust Biomarker Panel Diagnoses Pancreatic Cancer in Urine

Noninvasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available, but a set of urinary proteins have been identified that are able to distinguish patients with early-stage PDAC from healthy individuals.

Timely detection of PDAC is, however, hampered by several factors such as lack of specific clinical symptoms in the early stage of the disease, insufficient sensitivity of current imaging modalities and, despite intensive efforts, lack of accurate body fluid-based biomarkers of early-stage disease.

Scientists at Barts Cancer Institute (London, UK) and an international team of collaborators, analyzed 192 urine samples from patients with pancreatic cancer, alongside 92 samples from patients with chronic pancreatitis and 87 samples from healthy individuals. The team also assessed 117 additional samples from patients with other benign and malignant liver and gall bladder conditions for further validation.

Urine samples were processed and run on 4% to 12% mini-gels (Invitrogen; Carlsbad, CA, USA) and female and male urine specimens were analyzed separately. Gel slices were digested robotically with trypsin and resultant peptides analyzed by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS) using a nanoAcquity (Waters; Milford, MA, USA) interfaced to a LTQ Orbitrap XL tandem mass spectrometer (Thermo Fisher; Waltham, MA USA). Quantitative enzyme-linked immunosorbent assays (ELISA) were performed to detect certain proteins.

The team identified around 1,500 proteins in the urine samples. Three of these, Lymphatic Vessel Endothelial Hyaluronic Acid Receptor 1 (LYVE1), Regenerating Islet-Derived 1 Alpha (REG1A) and Trefoil Factor 1 (TFF1) were found at significantly higher levels in the urine samples of patients with pancreatic cancer, compared with the samples from healthy individuals. Patients with chronic pancreatitis, however, had much lower levels of all three proteins in their urine than patients with pancreatic cancer. Combining all three proteins to form a "robust panel," the team found they were able to diagnose stage 1 and 2 pancreatic cancer from patients' urine with more than 90% accuracy.

The authors concluded this urine screening test being completely noninvasive and inexpensive, could, upon further validation, and when coupled with timely surgical intervention, lead to a much improved outcome in patients with high risk of developing PDAC. This year, around 48,960 people in the US will be diagnosed with pancreatic cancer, and more than 40,000 individuals will die from the disease.

Tatjana Crnogorac-Jurcevic, MD, PhD, the senior author of the study, said, “We've always been keen to develop a diagnostic test in urine as it has several advantages over using blood. It's an inert and far less complex fluid than blood and can be repeatedly and noninvasively tested. This is a biomarker panel with good specificity and sensitivity and we're hopeful that a simple, inexpensive test can be developed and be in clinical use within the next few years.” The study was published on August 1, 2015, in the journal Clinical Cancer Research.

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Barts Cancer Institute 
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