Johns Hopkins scientists said they had developed a blood test that spots tumor–specific DNA and protein biomarkers for early–stage pancreatic cancer. The combined “liquid biopsy” identified the markers in the blood of 221 patients with the early–stage disease. Their results, published online in the Proceedings of the National Academy of Sciences journal, show that detection of markers from both DNA and protein products of DNA was twice as accurate at identifying the disease as detection of DNA alone.

"Most early–stage pancreatic cancers are found incidentally during an imaging scan and generally cause no symptoms," said Jin He, MD, assistant professor of surgery at the Johns Hopkins University School of Medicine. "If this test's performance is validated in larger studies, it could be used to identify patients with early, asymptomatic pancreatic cancer.”

While their test is not ready to be used outside of a research setting, they said, mutated DNA of the type that is shed from tumors and found in blood is “exquisitely specific” for cancer. Studies by Vogelstein’s team and others have shown that DNA can be identified in the blood of more than 85 percent of patients with advanced cancers. However, the sensitivity of detecting such small bits of DNA in the blood of patients with early cancers, without prior knowledge of the genetic status of the cancers, was unknown prior to this study, said the scientists.

In their new study, blood and tumor tissue samples were collected from 221 men and women, mostly Caucasians, with stage I and II pancreatic cancers who underwent surgery to remove their pancreas at hospitals in Australia, Korea, Indiana, Pittsburgh, the Mayo Clinic, Rochester, Memorial Sloan Kettering in New York and The Johns Hopkins Hospital. Another 182 people with no known history of cancer, autoimmune disease or chronic kidney disease donated their blood for the study.

The scientists were able to identify 66 of the 221 patients, or 30 percent, with early–stage pancreatic cancer by using their blood screening tool to sift for mutations in the DNA of the KRAS gene alone, an early marker of pancreatic cancer development.

Their goal, however, was to improve the 30 percent detection rate, find more early cancers and avoid false positives in people without the disease, said Joshua Cohen, an PhD postgraduate student in Vogelstein’s lab who worked on the study.

So, they turned to protein biomarkers circulating in the blood. Of special interest to the researchers was the protein biomarker CA19–9. It’s used to monitor patients with pancreatic cancer for recurrence. But the level of CA19–9 used for recurrence monitoring is low (37 units/mL), because physicians want to pinpoint regrowing cancers quickly.

Some people without cancer may also have low levels of the protein, such as those with gallstones. For screening purposes, the level of CA19–9 needed to be much higher (100 units/mL).

When the scientists looked only for CA19–9 in the blood of their study participants, they found it in 109 of the 221 patients (49 percent). However, when they combined detection of KRAS mutations, CA19–9 and three other protein biomarkers, the scientists correctly identified pancreatic cancer in 141 of the 221 patients (64 percent). In contrast, only one individual among their control group of 182 people without cancer had elevation of one of the five biomarkers.

Vogelstein’s team used a system of molecular barcoding that they developed to ensure that each KRAS mutation they detected was real and not an artifact.

Nick Papadopoulos, professor of oncology at the Johns Hopkins Kimmel Cancer Center, estimates that the cost of a screening test based on the approach described in this study would be between that of mammography and colonoscopy.