A Duke University research team has identified a set of biomarkers that could help distinguish whether cysts on the pancreas are likely to develop into pancreatic cancer or remain benign.
The National Cancer Institute-funded study, published Friday in the journal Science Advances, marked a first step toward a clinical approach for classifying lesions on the pancreas that are at the highest risk of becoming cancerous, potentially enabling their removal before they begin to spread.
Pancreatic cancer, which is on the rise, is notorious for silently growing before being discovered, often incidentally, during abdominal scans. If current trajectories continue, it may become the second-leading cause of cancer death in the U.S. within the next few years. While the cause of the cancer’s increased prevalence is unknown, some studies suggest inflammation may play a role. Current diagnostic strategies -- including clinical, radiographic, laboratory, endoscopic, and cytologic analysis -- have an overall accuracy of approximately 60%. However, even when detected at its earliest stage, the cancer has invariably shed cells throughout the body, causing it to metastasize.
Rather than treating the cancer, the researchers focused instead on preventing this often-fatal disease from developing in the first place. They studied precancerous cysts, called intraductal papillary mucinous neoplasms, or IPMNs. Previous methods to characterize IPMNs have not been able to identify highly accurate cancer risk markers. While most IPMNs never advance to pancreatic cancer, the team sought to distinguish those that were most likely to progress.
The researchers obtained tissue specimens from 12 patients who underwent pancreatectomy for IPMN between 2017 and 2021. They used a sophisticated molecular biology tool called digital spatial RNA profiling to home in on specific areas of the cysts with high-grade dysplasia or low-grade dysplasia -- areas of abnormal cell growth. The profiling tool allowed them to choose individual groups of cells for analysis, enabling them to identify a host of genetic mutations that both fuel and potentially suppress pancreatic cancer development. The team also identified markers for discriminating between the two leading variants of IPMN and found distinct markers for defining a third common variant that generally results in less-aggressive disease. They hypothesized that their biomarker-based approach could facilitate preventive surgeries to remove the cysts most likely to progress, thus decreasing the chances of developing pancreatic cancer.
“We found very distinct markers for high-grade cell abnormalities, as well as for slow-growing subtypes,” senior author Dr. Peter Allen, a surgical oncologist at Duke University School of Medicine, said in a statement. “Our work now is focusing on finding it in the 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 spreads.”