Novel 4-Biomarker Panel Improves Early Detection of Pancreatic Cancer

A 4-biomarker blood panel consisting of aminopeptidase N (ANPEP), polymeric immunoglobulin receptor (PIGR), CA19-9, and thrombospondin-2 (THBS2) significantly enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) compared with measuring CA19-9 levels alone, according to findings from a study published in Clinical Cancer Research.¹ The diagnostic may address a major hurdle in oncology by identifying malignancy at localized, early stages when 5-year survival rates are significantly higher than at the metastatic stage.

The 4-protein biomarker panel demonstrated superior performance over the current clinical standard, CA19-9 alone, across multiple independent cohorts. In the primary validation phases, the panel achieved an area under the curve (AUC) of 0.97 in the Mayo Clinic cohort and 0.96 in the University of Pennsylvania cohort when comparing stage I and II PDAC with healthy controls. An AUC of 1.0 indicates a perfect test for distinguishing between the 2 groups.

Data revealed that the panel was also highly effective in differentiating cancer from benign pancreatic conditions, a common clinical challenge. In the Mayo cohort, the panel yielded an AUC of 0.87 for early-stage PDAC and 0.91 for all stages. Specifically, the 4-biomarker panel correctly detected 91.9% of pancreatic cancers across all stages and 87.5% of early-stage cases. In contrast, testing for CA19-9 alone identified 82.7% of overall PDAC cases and 76.2% of early-stage cases. Statistical significance was achieved for detecting all-stage pancreatic cancer; however, statistical significance was not achieved for detecting early-stage pancreatic cancer despite the numerical improvement of 11.3%.

“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,” stated Kenneth S. Zaret, PhD, professor at the Perelman School of Medicine at the University of Pennsylvania and senior author of the study, in a news release.² “Our goal was to look for biomarkers in the blood that appear in [patients with] early-stage PDAC to catch the disease early.”

The study utilized retrospective plasma samples from 2 large independent cohorts—the Mayo Clinic (n = 537) and the University of Pennsylvania (n = 135)—to validate the performance of the biomarker signatures. Researchers initially identified ANPEP and PIGR as novel candidates by comparing protein levels in patients with early-stage disease against those without cancer. These 2 proteins were then combined with the established markers CA19-9 and THBS2 to create the finalized 4-protein panel.

Zaret added, “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.”²

Patients with confirmed pancreatic cancer, healthy individuals, and those with benign pancreatic disease were included in separate cohorts in the study.

The study’s end points included the panel's AUC, sensitivity, and specificity in identifying PDAC. One limitation of the study was the lack of inclusion of patients with increased risk for pancreatic cancer. This would have included patients with a family history of the disease, germline BRCA mutations, or new-onset diabetes.

“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,” Zaret concluded.²

References

1. Krusen BM, Gimotty PA, Donahue G, et al. Improving a plasma biomarker panel for early detection of pancreatic ductal adenocarcinoma with aminopeptidase N (ANPEP) and polytmeric immunoglobin receptor (PIGR). Clinical Cancer Research. Published online January 28, 2026. doi:10.1158/1078-0432.CCR-25-3297
2. Investigational blood biomarker panel may improve detection of pancreatic cancer. News release. AACR. January 28, 2026. Accessed January 28, 2026. https://tinyurl.com/35c7vzwe