Research Spotlight: Using Extracellular Vesicles for Earlier Detection of Bile Duct Cancer

Hyungsoon Im, PhD, an investigator in the Center for Systems Biology at Massachusetts General Hospital and an assistant professor of Radiology at Harvard Medical School, is the senior author of a new study in Advanced Sciences, Plasmon-Enhanced Single Extracellular Vesicle Analysis for Cholangiocarcinoma Diagnosis.  

What Question Were You Investigating?

Cholangiocarcinoma (CCA), cancer that forms in the bile ducts, is a fatal disease that is often detected after it has spread too far to be surgically removed. There are currently no effective biomarkers or diagnostic tools to detect CCA with high confidence.

Extracellular vesicles (EVs) are small particles released from cells that are used to transport different proteins, nucleic acids, lipids and other materials between cells.

We wanted to see if molecular analysis of extracellular vesicles (EVs) in human bile samples could accurately detect patients with cholangiocarcinoma from patients with other benign or inflammatory conditions.

What Was Your Approach?

We first developed a nanoplasmonic sensing technology, named FLEX (fluorescence-amplified extracellular vesicle sensing technology). FLEX enables multiplexed single EV analysis through a simple and rapid detection assay.

After validation in cell line-derived EVs, we applied the technology to human bile samples collected through an endoscopic retrograde cholangiopancreatography (ERCP) procedure. 

What Did You Find?

1. The FLEX chips could sensitively detect small tumor-derived EVs that were missed by conventional EV methods.
2. The molecular analysis of tumor-derived EVs could accurately detect CCA patients with significantly better accuracy (93%) than the current ERCP-based tissue biopsies or serum biomarkers.

What Are the Clinical Implications?

The new method has the potential to detect CCA at earlier stages than is currently possible, which could significantly improve the five-year survival rate for the disease, which remains under 20%.

The molecular analysis of a bile sample could further improve the diagnostic accuracy of the current gold standard pathology diagnosis through ERCP.

With ERCP, up to 20% of brush biopsies are found inconclusive, requiring repeated procedures and delaying treatment.

Paper Cited:

Jeong, M. H., Son, T., Tae, Y. K., Park, C. H., Lee, H. S., Chung, M. J., Park, J. Y., Castro, C. M., Weissleder, R., Jo, J. H., Bang, S., & Im, H. (2023). Plasmon-Enhanced Single Extracellular Vesicle Analysis for Cholangiocarcinoma Diagnosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e2205148. Advance online publication. https://doi.org/10.1002/advs.202205148

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.