A research team at Duke Health has identified a set of biomarkers that can help differentiate whether cysts on the pancreas are likely to develop into cancer or remain benign.
Appearing online March 17 in the magazine advance science, This finding represents an important first step towards a clinical approach to classify lesions on the pancreas at high risk of cancer, potentially enabling them to be removed before they begin to spread.
If successful, the biomarker-based approach could address the biggest barrier to reducing the chance of developing pancreatic cancer, which is on the rise and is notorious for growing silently before being discovered, often incidentally, during abdominal scans.
“Even when pancreatic cancer is caught in its early stages, it almost always sheds cells throughout the body, and the cancer comes back,” said senior investigator Peter Allen, MD, chief of surgical oncology in the hospital’s department of surgery. Duke University School of Medicine.
“That’s why we shifted our focus to these precancerous cysts, known as internal papillary mucinous neoplasms, or IPMNs,” Allen said. “Most IPMNs will never progress to pancreatic cancer, but by distinguishing which ones will progress, we create an opportunity to prevent the development of an incurable disease.”
Allen and colleagues used a cutting-edge molecular biology tool called Digital Spatial RNA Profiling to match specific areas of the cyst with high- and low-grade areas of abnormal cell growth.
Previous methods of characterizing IPMNs were less accurate and were not able to identify particularly accurate markers of cancer risk. However, digital spatial profiling allows researchers to select individual groups of cells for analysis. This enabled the Duke researchers to identify a set of genetic mutations that fuel and possibly inhibit the development of pancreatic cancer.
The team also identified markers to distinguish between the two main variants of IPMN and found markers to identify a third common variant that generally results in less aggressive disease.
“We found very distinct markers for high-grade cell abnormalities, as well as for slow-growing subtypes,” Allen said. “Our work is now focused on finding it in cyst fluid. If we can identify these unique markers in cyst fluid, it could provide the basis for a protein biopsy that would guide whether we should remove the cyst before cancer develops and metastasizes.”
Allen said current diagnostic strategies — including clinical, radiographic, laboratory, endoscopy, and cytological analysis — have an overall accuracy of about 60 percent.
“Pancreatic cancer is on the rise and, if current trajectory continues, will become the second leading cause of cancer death in the United States in the next few years,” Allen said, noting that it is not known what is driving the cancer’s increasing prevalence. .
He said some studies suggest inflammation plays a role. A clinical trial at Duke, led by Allen, is testing whether anti-inflammatory therapy can reduce cancer progression in patients with IPMN.
In addition to Allen, study authors include Matthew Kaier, Changguan Shi, Austin M. Eckhoff, Ashley Fletcher, and Daniel B. Nussbaum.
The study received funding support from the National Cancer Institute (RO1 CA182076).
