A recent study has found that a four-biomarker blood panel can improve the detection of pancreatic ductal adenocarcinoma (PDAC) compared to testing for CA19-9 alone. The research, led by Kenneth S. Zaret, PhD, professor at the Perelman School of Medicine at the University of Pennsylvania, was published in Clinical Cancer Research.
Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, making up about 95% of cases. Early detection is crucial: when found at a localized stage, the five-year survival rate is around 44%. However, if diagnosed after metastasis, this rate drops to 3%. Most cases are currently detected at late stages.
"Pancreatic cancer usually doesn't present with symptoms until it's too late for surgery, when the cancer has already metastasized to other parts of the body," said Zaret. "Our goal was to look for biomarkers in the blood that appear in early-stage PDAC patients, to catch the disease early," he explained.
CA19-9 is commonly used to monitor pancreatic cancer but is not recommended as a standalone screening tool because it can be elevated in benign conditions and may be low even in some people with pancreatic cancer. THBS2 is an investigational biomarker that can complement CA19-9 but has shown mixed results for early detection. "CA19-9 is widely used to monitor diagnosed pancreatic cancer but isn't recommended as a standalone screening test—benign conditions can elevate it in some people, while others may have low levels, even if they have pancreatic cancer. THBS2 is investigational and can complement CA19-9, but its prediagnostic performance has been mixed," said Zaret.
To identify new biomarkers, researchers analyzed plasma samples from two cohorts: 537 from Mayo Clinic and 135 from the Hospital of the University of Pennsylvania. These included patients with confirmed pancreatic cancer, healthy individuals, and those with benign pancreatic disease. They identified two proteins—aminopeptidase N (ANPEP) and polymeric immunoglobulin receptor (PIGR)—with elevated levels in early-stage PDAC patients.
The team then developed a panel measuring ANPEP, PIGR, CA19-9, and thrombospondin-2 (THBS2). In both cohorts studied, this four-biomarker panel achieved area under curve (AUC) values of 0.97 and 0.96 when distinguishing between early-stage PDAC and healthy controls—a near-perfect result on this scale.
The panel also distinguished between cancer and benign conditions with an AUC of 0.87 for early-stage PDAC and 0.91 for all stages in one cohort. It correctly detected 91.9% of all PDAC cases and 87.5% of early-stage cases across all stages studied—compared to CA19-9 alone which identified 82.7% overall and 76.2% of early-stage cases.
"With the addition of ANPEP and PIGR, the panel helps to overcome known limitations associated with CA19-9 and THBS2 testing—such as patients who genetically underexpress CA19-9 or tumors that present as different molecular subtypes—and could therefore reduce the number of missed cancer cases while keeping false positives low," said Zaret.
If these findings are confirmed through larger prospective studies, Zaret explained that "the four-biomarker blood panel could improve the ability to identify which individuals with a high risk for pancreatic cancer would benefit from follow-up imaging," potentially allowing earlier diagnosis.
However, there are limitations noted by Zaret: "One limitation of this study is that the cohorts did not include individuals at increased risk for pancreatic cancer... introducing a bias in test performance." He also mentioned that because this was a retrospective study using previously collected samples rather than following participants forward over time, larger prospective studies are needed to confirm real-world screening effectiveness.
