New Biomarkers Could Be “More Accurate” Predictors of Pancreatic Cancer

A new study identifies a set of biomarkers that could help clinicians to predict whether pancreatic cysts will remain benign or develop into cancer. The research, led by Duke Health scientists, is published in Science Advances.

A “silent” killer

Pancreatic ductal adenocarcinoma – or pancreatic cancer – is often referred to as a “silent” killer, as symptoms rarely appear until a patient’s disease is at an advanced stage. Treatment options for pancreatic cancer may include surgical resection, chemotherapy or a combination of different approaches. However, if a patient’s cancer is extensive, the likelihood of such therapeutic approaches being effective declines.

“Even when pancreas cancer is detected at its earliest stage, it almost always has shed cells throughout the body, and the cancer returns,” says Dr. Peter Allen, physician and chief of the Division of Surgical Oncology at in the Department of Surgery at Duke University School of Medicine.

Clinically valid biomarkers that can identify patients at risk of developing pancreatic cancer are lacking. In the new study, Allen and colleagues at Duke Health explored the biomarker potential of intraductal papillary mucinous neoplasms – or IPMNs – which are cystic legions of the pancreas.

IPMNs are categorized as either low risk for progression, also known as low-grade dysplasia (LGD), or high risk for progression (high-risk dysplasia, HGD). “Most IPMNs will never progress to pancreas cancer, but by distinguishing which ones will progress, we are creating an opportunity to prevent an incurable disease from developing,” Allen says.

Towards a protein biopsy

While previous work has sought to characterize IPMNs, they have relied on single-cell RNA sequencing (RNA-seq), which characterizes cell populations within bulk tissues but cannot provide information on the cells’ spatial relationships.

Allen and team adopted a method known as digital spatial RNA profiling on 12 patient specimens. “This technology offers precise comparison of gene expression among user-defined disease regions without the need for cumbersome microdissection,” the authors explain in the paper, adding “We recently used this technology to explore the composition of immune cells within the IPMN tumor microenvironment. Here, we report spatial RNA profiling of ductal epithelium across subtypes to determine markers of dysplasia and identify biological processes that associate with malignant progression.”

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Using spatial RNA profiling, the researchers could dig deeper into the molecular biology of the cysts, identifying specific areas that demonstrated high- and low-grade areas of abnormal cell growth. They discovered biomarkers that could distinguish between the two types of IPMNs, and also found markers for a third type that generally produces a less aggressive disease.

"We found very distinct markers for high-grade cell abnormalities, as well as for slow-growing subtypes,” Allen explains. “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.”

Taken from Technology Networks. 

A protein biopsy could help overcome the accuracy issues of existing diagnostic strategies, which include radiographic, clinical, laboratory, endoscopic and cytologic analyses. “Pancreatic cancer is on the rise and, if the current trajectory continues, it will become the second-leading cause of cancer death in the United States in the next few years,” Allen emphasizes.

“The idea that high-risk IPMN could be detected before the development of HGD would certainly alter our clinical approach to the disease. Expanded spatial profiling that includes regions of normal ductal epithelium and invasive carcinoma could address this intriguing possibility,” the researchers conclude.

Reference: Iyer MK, Shi C, Eckhoff AM, Fletcher A, Nussbaum DP, Allen PJ. Digital spatial profiling of intraductal papillary mucinous neoplasms: Toward a molecular framework for risk stratification. Sci Adv. 9(11):eade4582. doi:10.1126/sciadv.ade4582.

This article is a rework of a press release issued by Duke Health. Material has been edited for length and content.