An Investigational Blood Test May Improve Detection of Pancreatic Cancer
The four-biomarker blood panel enhanced the detection of pancreatic cancer compared to standard testing.
The pancreas aids with digestion and produces hormones, such as insulin and glucagon, that help regulate blood sugar levels. When cancer develops in the pancreas, known as pancreatic cancer, it is often found after the disease has metastasized, leading to a poor prognosis with only a 3% five-year survival rate. However, when detected at a localized, early-stage, the five-year relative survival jumps to about 44%.
Pancreatic ductal adenocarcinoma (PDAC), which forms from the exocrine cells in the pancreas, is the most common form of pancreatic cancer, accounting for about 95% of cases.
Researchers at the University of Pennsylvania set out to look for biomarkers in the blood that appear in early-stage PDAC to help clinicians catch the disease earlier. Their results were published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).
Looking to Blood for Answers
CA19-9 is a protein that is released into the blood by both cancer cells and normal pancreatic cells, and elevated levels of CA19-9 in the blood can be a sign of pancreatic cancer or other diseases. THBS2 is a protein that is expressed in PDAC tumor tissue, and when screened for in blood alongside CA19-9 using a bioassay, enables the test to better discriminate between PDAC and healthy patients, according to previous work from Kenneth S. Zaret, PhD, senior author of the study and professor at the Perelman School of Medicine at the University of Pennsylvania, and colleagues. However, Dr. Zaret noted that these biomarkers are insufficient for routine 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,” he said.
To identify novel biomarkers of pancreatic cancer, Dr. Zaret and colleagues analyzed plasma samples from two cohorts: 537 samples from the Mayo Clinic (Mayo) and 135 from the Hospital of the University of Pennsylvania (Penn). The cohorts included patients with confirmed pancreatic cancer, healthy individuals, and patients with benign pancreatic disease, which enabled the researchers to evaluate the ability of candidate biomarkers to differentiate between pancreatic cancer and benign conditions that could mimic cancer.
By comparing protein levels across the plasma samples, the researchers identified two proteins, ANPEP and PIGR, that showed elevated levels in samples from patients with early-stage PDAC, compared with samples from patients without cancer.
Dr. Zaret and colleagues then developed a panel that measured the blood levels of four biomarkers: the newly identified ANPEP and PIGR, along with the previously known biomarkers CA19-9 and THBS2.
A Potentially Valuable Resource for Clinicians
Across the two independent cohorts, Mayo and Penn, the four‑biomarker blood panel showed area under curve (AUC) values of 0.97 and 0.96, respectively, when comparing stage 1-2 PDAC and healthy controls. The AUC is a measure of the test’s ability to distinguish between two groups, with 1.0 being a perfect score.
The panel was also able to distinguish cancer from benign pancreatic conditions with an AUC of 0.87 for early‑stage PDAC and 0.91 for all stages in the Mayo cohort.
The four-biomarker panel correctly detected 91.9% of pancreatic cancers across all stages and 87.5% of early‑stage cases, compared to testing for the CA19-9 biomarker alone, which identified 82.7% of the PDAC cases overall and 76.2% of the early-stage cases. The improvement in all-stage cancer detection was statistically significant, whereas the gain in early‑stage detection did not reach statistical significance in spite of the 11.3% improvement in sensitivity.
If confirmed in larger, prospective studies, 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, explained Dr. Zaret, adding that this could allow clinicians to detect more pancreatic cancers at an earlier, more treatable stage.
“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.