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Urine biomarkers accurately identify early-stage pancreatic cancer
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Researchers have developed a three-biomarker panel that can detect early-stage pancreatic ductal adenocarcinoma through urine analysis, which could lead to a noninvasive screening test for high-risk individuals.
“We’ve always been keen to develop a diagnostic test in urine as it has several advantages over using blood,” Tatjana Crnogorac-Jurcevic, MD, PhD, from Barts Cancer Institute, Queen Mary University of London, said in a press release. “It’s an inert and far less complex fluid than blood and can be repeatedly and noninvasively tested. It took a while to secure proof of principle funding in 2008 to look at biomarkers in urine, but it’s been worth the wait for these results. 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.”
For the discovery phase of the study, Crnogorac-Jurcevic and colleagues used GeLC/MS/MS analysis to assay proteomes from urine samples from six patients with pancreatic ductal adenocarcinoma, six with chronic pancreatitis and six healthy controls. They then selected LYVE1, REG1A and TFF1 as biomarker candidates and validated them using ELISA assays to analyze 488 urine samples from a multicenter cohort (192 from patients with pancreatic ductal adenocarcinoma, 92 with chronic pancreatitis, 87 healthy volunteers and 117 from patients with other benign and malignant liver and gall bladder conditions).
“For a cancer with no early-stage symptoms, it’s a huge challenge to diagnose pancreatic cancer sooner, but if we can, then we can make a big difference to survival rates,” Nick Lemoine, MD, PhD, FRCPath, FMedSci, director of Barts Cancer Institute, said in the release. “With pancreatic cancer, patients are usually diagnosed when the cancer is already at a terminal stage, but if diagnosed at stage 2, the survival rate is 20%, and at stage 1, the survival rate for patients with very small tumors can increase up to 60%.”
Each biomarker and the three-biomarker panel were evaluated with their performance in differentiating between pancreatic ductal adenocarcinoma patients (all stages or early stages 1-2) and controls, and for each comparison 70% of participants were randomly assigned to a training dataset, and the rest to a validation dataset.
For pancreatic ductal adenocarcinoma urine samples compared with samples from healthy controls, the panel performed with areas under the receiver operating characteristic curves (AUCs) of 0.891 (95% CI, 0.847-0.935) in the training dataset and 0.921 (95% CI, 0.863-0.978) in the validation dataset. For stage 1 to 2 pancreatic ductal adenocarcinoma urine samples compared with healthy controls, AUCs were 0.9 (95% CI, 0.843-0.957) and 0.926 (95% CI, 0.843-1). For stage 1 to 2 pancreatic ductal adenocarcinoma urine samples compared with healthy controls with matching plasma CA19.9, AUCs for the biomarker panel were 0.973 (95% CI, 0.947-0.999) vs. 0.88 (95% CI, 0.81-0.95) for CA19.9 alone. The addition of CA19.9 to the panel increased the AUC to 0.991 (95% CI, 0.979-1), but this did not improve the comparison of stage 1 to 2A pancreatic ductal adenocarcinoma to healthy controls.
“This is an exciting finding and we hope to see this research taken forward into a much needed early diagnostic test,” Maggie Blanks, CEO of the Pancreatic Cancer Research Fund, said in the release. “Early diagnosis is an important part of our overall efforts against this aggressive cancer, alongside developing new treatments to tackle the disease once diagnosis is made. It underlines the importance of increased research efforts to help improve survival rates.” – by Adam Leitenberger
Disclosure: The researchers report no relevant financial disclosures.
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