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Published July 16, 2022

Developing an exosome-based liquid-biopsy signature for the noninvasive and robust detection of PDAC

The incidence of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is rising worldwide. It is predicted to become the second leading cause of cancer-associated mortality within the next decade in United States because most patients present with a cancer that cannot be removed by surgery at the time of their diagnosis. There is a clear need for an earlier detection method that would offer patients more opportunities for treatment and survival.

Cancer cells can sometimes be distinguished from normal cells by displaying abnormal levels and types of carbohydrate structures on their surfaces, known as tumor-associated carbohydrate antigens. But measurement of carbohydrate antigen 19-9 levels in PDAC are not sensitive and specific enough for early detection, so researchers are looking for alternate molecular diagnostic biomarkers.

Emerging evidence suggests that material carried by exosomes – tiny sac-like structures formed inside cells that contain some of the cell’s proteins, DNA and RNA – can offer a platform for developing PDAC-specific biomarkers.

A multicenter research team that included John Bolton, MD, Chairman Emeritus of the Department of Surgery at Ochsner Medical Center - New Orleans, sequenced the microRNA (a family of molecules that helps cells control gene expression) off 44 patients diagnosed with early-stage PDAC and 57 patients without the disease. Ochsner’s data contribution to the study was assisted by Dana Feist, clinical research coordinator at Ochsner Medical Center - New Orleans and Sophia Turner, associate clinical research coordinator, located at the St. Tammany Cancer Center - A Campus of Ochsner Medical Center in Covington, LA.

The researchers identified a panel of 30 overexpressed microRNAs in PDAC samples, which they whittled down to 13 markers through subsequent assays. These markers successfully identified patients with all stages of PDAC, including early-stage PDAC, even those that were negative for carbohydrate antigen 19-9.

Through these studies, the researchers developed an exosome-based liquid-biopsy signature that can be used for the noninvasive and robust detection of patients with PDAC, even in early stages. People with multiple risk factors for developing PDAC – those with a family history of PDAC or a specific hereditary background including hereditary pancreatitis or Peutz-Jeghers syndrome – could be eligible for this noninvasive and inexpensive exosome-based test, along the traditional carbohydrate antigen test, in the hope that cancers could be detected and treated earlier.