Pancreatic cancer has a poor prognosis, with only about 10% of patients living longer than five years after diagnosis. However, doctors believe survival could improve significantly if the disease is caught earlier, when treatment is more effective. Despite this, there are currently no reliable screening tools available to detect pancreatic cancer in its early stages.

Testing Existing and New Blood Biomarkers

To address this gap, scientists from the University of Pennsylvania Perelman School of Medicine, Philadelphia, and Mayo Clinic, Rochester, Minnesota, analyzed blood samples from individuals with and without pancreatic cancer. They evaluated several biomarkers, including carbohydrate antigen 19-9 (CA19-9), commonly used to monitor treatment response, and thrombospondin 2 (THBS2), another previously studied marker.

Individually, these markers have limitations. CA19-9 levels can rise in non-cancerous conditions like pancreatitis or bile duct obstruction, and some people do not produce the marker at all due to genetic differences. As a result, neither marker alone is reliable enough for screening.

Newly Identified Proteins Improve Detection

By examining stored blood samples, the researchers identified two additional proteins that appear to be elevated in people with early-stage pancreatic cancer: aminopeptidase N (ANPEP) and polymeric immunoglobin receptor (PIGR). These newly identified biomarkers showed clear differences between cancer patients and healthy individuals.

When combined with CA19-9 and THBS2, the four-marker panel demonstrated strong performance. It correctly distinguished pancreatic cancer cases from non-cases 91.9% of the time across all stages, with a false positive rate of 5% in non-cases. For early-stage (stage I/II) cancer, the test detected 87.5% of cases.

“By adding ANPEP and PIGR to the existing markers, we’ve significantly improved our ability to detect this cancer when it’s most treatable,” said the study’s lead investigator, Kenneth Zaret, Ph.D., University of Pennsylvania’s Perelman School of Medicine.

Distinguishing Cancer From Other Conditions

An important advantage of the test is its ability to differentiate pancreatic cancer from other non-cancerous pancreatic conditions, including pancreatitis. This helps reduce the risk of misdiagnosis and unnecessary concern for patients.

Next Steps Toward Screening

“Our retrospective study findings warrant further testing in larger populations, particularly in people before they show symptoms,” Zaret said. “Such ‘prediagnostic’ studies would help determine if the test could be used as a screening tool for people at high risk of developing the disease based on family history, genetic screening results or personal history of pancreatic cysts or pancreatitis.”

The study was supported by NIH grants U01CA210138, P50CA102701, S10 OD023586-01, P30 DK020579, UL1 TR002345, P30CA091842, and U01CA210138.