A study from the Perelman School of Medicine at the University of Pennsylvania has found that a blood test measuring four specific proteins may improve the detection of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The research, published in Clinical Cancer Research, evaluated a biomarker panel consisting of ANPEP, PIGR, CA19-9, and THBS2.
Pancreatic ductal adenocarcinoma accounts for about 95 percent of pancreatic cancer cases. Early detection is critical because patients diagnosed at an early stage have a five-year relative survival rate of approximately 44 percent. In contrast, this rate drops to 3 percent when the disease has metastasized.
“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 Kenneth S. Zaret, PhD, senior author and professor of Cell and Developmental Biology. “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 currently used to monitor diagnosed pancreatic cancer but is not recommended as a standalone screening test due to its limitations; benign conditions can also elevate it or some patients may show low levels despite having cancer. THBS2 can complement CA19-9 but its performance before diagnosis has been inconsistent.
“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,” Zaret said.
The research team analyzed plasma samples from two groups: one from Mayo Clinic with 537 samples and another from Penn with 135 samples. These included individuals with confirmed pancreatic cancer, healthy participants, and those with benign pancreatic diseases. The researchers identified ANPEP and PIGR as proteins elevated in early-stage PDAC patients compared to those without cancer.
The new panel combining ANPEP, PIGR, CA19-9, and THBS2 demonstrated high accuracy in distinguishing early-stage PDAC from healthy controls—with area under curve (AUC) values of 0.97 (Mayo) and 0.96 (Penn). The panel also differentiated between cancerous and benign conditions with AUC values up to 0.91 for all stages in one cohort.
When comparing detection rates across all stages of PDAC using this four-protein panel versus testing only for CA19-9:
– The panel correctly detected 91.9 percent of all PDAC cases versus 82.7 percent by CA19-9 alone.
– For early-stage cases specifically, it identified 87.5 percent compared to CA19-9’s 76.2 percent.
While overall improvement was statistically significant for all stages combined, gains for early-stage detection did not reach statistical significance despite showing higher sensitivity.
Zaret noted that if validated by larger studies over time, this approach could help identify high-risk individuals who would benefit from further imaging tests: “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,” he said.
However, he pointed out two main limitations: neither cohort included people at increased risk due to family history or genetic factors such as BRCA mutations; also, since this was a retrospective study design rather than prospective tracking over time, further work is needed before clinical adoption.
Funding sources include grants from organizations such as the National Institutes of Health and Penn Pancreatic Cancer Research Center among others. Zaret reported no conflicts of interest.
