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Exosomes shuttle molecular cargoes from one cell to another as a form of intercellular communication.

Novel Exosome-Based Liquid Biopsy Detects Pancreatic Cancer

When combined with CA 19-9, the novel biopsy accurately detected 97 percent of stage 1–2 pancreatic cancers

American Association for Cancer Research
Published:Apr 08, 2024
|3 min read
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SAN DIEGO, CA — An investigational exosome-based liquid biopsy accurately detected 97 percent of stage 1–2 pancreatic cancers when combined with the biomarker CA 19-9. “Pancreatic cancer is one of the most fatal malignancies, in large part because the majority of patients are diagnosed only after the cancer has already metastasized,” said Ajay Goel, PhD, senior author of the study and the chair of the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope.

While the five-year relative survival rate for patients diagnosed at the earliest stages—before the cancer has spread from the pancreas—is 44.3 percent, it is only 3.2 percent for those diagnosed with metastatic disease. “It is of utmost importance to diagnose patients as early as possible so they have the opportunity to receive potentially curative surgery and treatment,” Goel said.

Why exosome-based liquid biopsy?

Caiming Xu, MD, PhD, a postdoctoral fellow in Goel’s research group, added that early detection of pancreatic cancer remains challenging due to the nonspecific symptoms of the disease and because the pancreas is located deep within the abdomen, where it cannot be easily palpated during physical examination. Furthermore, existing biomarkers, such as CA19-9, are not reliable on their own to detect early-stage pancreatic cancer.

Goel, Xu, and colleagues explored the potential of an exosome-based liquid biopsy to detect pancreatic cancer at early stages. Liquid biopsies examine blood or other biological fluids for signs of cancer, such as genetic material or cells shed by tumors. The researchers developed a novel liquid biopsy approach that analyzed exosomes shed by cancerous and healthy cells into the bloodstream. Exosomes shuttle molecular cargoes from one cell to another as a form of intercellular communication.

“Exosomes retain the cytoplasmic content of the cell from which they were shed, essentially replicating the biology of their tissue of origin,” Xu explained. The researchers identified eight microRNAs that were uniquely found in exosomes shed from pancreatic cancers. They combined these with five cell-free DNA markers found in the blood of patients with pancreatic cancer to develop a signature associated with this disease.

Testing the pancreatic cancer molecular signature

The researchers previously tested the performance of their exosome-based liquid biopsy signature in a cohort of 95 individuals from either the United States or Japan, reporting a 98 percent pancreatic cancer detection rate. The latest study sought to evaluate the liquid biopsy in large, prospective cohorts from multiple institutions and countries.

The study enrolled individuals from:

  • Japan (150 with pancreatic cancer; 102 healthy donors),

  • the United States (139 with pancreatic cancer; 193 healthy donors),

  • South Korea (184 with pancreatic cancer; 86 healthy donors), and

  • China (50 with pancreatic cancer; 80 healthy donors).

The liquid biopsy signature was trained on information from the Japanese cohort and validated in the cohorts from the US, South Korea, and China. Goel, Xu, and colleagues reported that their liquid biopsy approach detected:

  • 93 percent of pancreatic cancers in the cohort from the US,

  • 91 percent of pancreatic cancers in the cohort from South Korea, and

  • 88 percent of pancreatic cancers in the cohort from China.

Further, when they combined their signature with the pancreatic cancer marker CA19-9, the liquid biopsy test accurately detected 97 percent of stage 1–2 pancreatic cancers in the US cohort. 

Liquid biopsy outperforms existing detection methods

Stage 1 pancreatic cancers are confined to the pancreas; some stage 2 cancers have spread to nearby lymph nodes but have not spread to distant sites. “We have established an exosome-based signature that combines exosomal microRNAs and cell-free DNA to robustly identify patients with early-stage pancreatic cancer,” said Xu.

“Our approach offers a liquid biopsy test superior to CA19-9 measurement alone for early-stage disease,” Goel added. “Moreover, we evaluated the effectiveness of our assay in several different populations, including populations of different ethnic and geographical backgrounds.”

While additional research is needed before this test can be deployed to the general population, the researchers noted that it might benefit certain groups with a high risk for pancreatic cancer, such as those with chronic pancreatitis, new-onset diabetes, or a family history of pancreatic cancer.

A limitation of the study was the number of Black individuals included in the study cohorts. Another limitation was the lack of an established microRNA control against which to normalize the levels of candidate microRNAs used to develop the signature.

- This press release was originally published on the American Association of Cancer Research website