Biomarker Panel to Screen for Pancreatic Cancer May be Possible
June 19, 2012
- Forty weak biomarkers must be identified.
- Disease heterogeneity makes single biomarker diagnostics problematic.
LAKE TAHOE, Nev. — The development of a highly accurate, blood-based pancreatic adenocarcinoma screen that would be accurate enough to test the general population for this deadly disease may not be far out of reach, according to data presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges
conference, held here June 18-21, 2012.
Matthew Firpo, Ph.D., a research assistant professor at the Huntsman Cancer Institute at the University of Utah, came to the conclusion that screening a panel of biomarkers might be effective by embracing the idea that pancreatic adenocarcinoma has vast genetic heterogeneity, meaning no single biomarker exists that is strongly correlated with its diagnosis across the population of people who develop the disease.
Although it is widely accepted that earlier detection of pancreatic adenocarcinoma would improve survival outcomes, research efforts to date have been unsuccessful at identifying a biomarker or biomarker panel that has a high diagnostic sensitivity.
“Any tool that we deploy in the general population to screen for this disease would have to be very accurate,” Firpo explained. “Because this cancer is rare, if everyone older than age 50 in the United States was screened with a test that was only 95 percent accurate, we would have more than three million people each year with a false positive identification of pancreatic adenocarcinoma.”
Therefore, Firpo said that any test for pancreatic adenocarcinoma deployed to the general population must have an accuracy of greater than 99 percent. To see if such levels of accuracy were possible, the researchers measured the levels of nine biomarkers of pancreatic adenocarcinoma in the blood of 117 healthy control participants, 58 participants with chronic pancreatitis and 159 patients with pancreatic adenocarcinoma.
Using a statistical model, they determined that many of these weak biomarkers present in those patients with pancreatic adenocarcinoma had 95 percent specificity for the disease, but, on average, only a 32 percent sensitivity.
“Based on the data, and specifying 99 percent specificity, it would take a panel of 40 biomarkers with 32 percent average sensitivity each and 95 percent specificity, of which seven biomarkers were above this threshold,” Firpo said.
The key to the study, according to Firpo, is accepting the fact that pancreatic adenocarcinomas are genetically heterogeneous. By developing a model that accounted for the heterogeneity they were able to get over 99 percent accuracy.
“Identifying 40 biomarkers is reasonable. We believe we can find 40 biomarkers that are weak classifiers of the disease,” he said. “That means that based on the current understanding of biomarkers that we have, there is hope for developing a panel that would have greater than 99 percent accuracy.”
Firpo said that the next step is to systematically identify 40 to 50 biomarkers that have these characteristics — 32 percent sensitivity and 95 percent specificity — or better.
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Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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