An exosome-based liquid biopsy shows promise for early detection of pancreatic cancer

An investigational exosome-based liquid biopsy precisely detected 97% of stage 1-2 pancreatic cancers when mixed with the biomarker CA 19-9, in line with analysis offered on the American Association for Cancer Research (AACR) Annual Meeting 2024held April 5-10.

“Pancreatic most cancers is likely one of the most deadly malignancies, largely as a result of the vast majority of sufferers are identified solely after the most cancers has already metastasized,” stated Ajay Goel, Ph.D., senior writer of the examine and the chair of the Division of Molecular Diagnostics and Experimental Therapeutics at Metropolis of Hope.

Whereas the five-year relative survival price for sufferers identified on the earliest phases—earlier than the most cancers has unfold from the pancreas—is 44.3%, it’s only 3.2% for these identified with metastatic illness. “It’s of utmost significance to diagnose sufferers as early as attainable in order that they have the chance to obtain probably healing surgical procedure and remedy,” Goel stated.

Caiming Xu, MD, Ph.D., a postdoctoral fellow in Goel’s analysis group, added that early detection of pancreatic most cancers stays difficult as a result of nonspecific signs of the illness and since the pancreas is positioned deep inside the stomach, the place it can’t be simply palpated throughout bodily examination. Moreover, current biomarkers, akin to CA19-9, aren’t dependable on their very own to detect early-stage pancreatic most cancers.

Goel, Xu, and colleagues explored the potential of an exosome-based liquid biopsy to detect pancreatic most cancers at early phases. Liquid biopsies look at blood or different organic fluids for indicators of most cancers, akin to genetic materials or cells shed by tumors. The researchers developed a novel liquid biopsy method that analyzed specialised vesicles referred to as exosomes, that are shed by cancerous and wholesome cells into blood. Exosomes shuttle molecular cargoes from one cell to a different as a type of intercellular communication.

“Exosomes retain the cytoplasmic content material of the cell from which they have been shed, basically replicating the biology of their tissue of origin,” Xu defined.

The researchers recognized eight microRNAs (small noncoding RNA molecules) that have been uniquely present in exosomes shed from pancreatic cancers. They mixed these with 5 cell-free DNA markers discovered within the blood of sufferers with pancreatic most cancers to develop a signature related to this illness.

The researchers beforehand examined the efficiency of their exosome-based liquid biopsy signature in a cohort of 95 people from both the US or Japan, reporting a 98% pancreatic most cancers detection price. The most recent examine sought to guage the liquid biopsy in giant, potential cohorts from a number of establishments and international locations.

The examine enrolled people from:

• Japan (150 with pancreatic most cancers; 102 wholesome donors);
• the US (139 with pancreatic most cancers; 193 wholesome donors);
• South Korea (184 with pancreatic most cancers; 86 wholesome donors); and
• China (50 with pancreatic most cancers; 80 wholesome donors).

The liquid biopsy signature was educated on data from the Japanese cohort and validated in cohorts from the US, South Korea, and China. Goel, Xu, and colleagues reported that their liquid biopsy method detected

• 93% of pancreatic cancers within the U.S. cohort;
• 91% of pancreatic cancers within the South Korean cohort and
• 88% of pancreatic cancers within the Chinese language cohort.

Additional, once they mixed their signature with the pancreatic most cancers marker CA19-9, the liquid biopsy take a look at precisely detected 97% of stage 1-2 pancreatic cancers within the U.S. cohort. Stage 1 pancreatic cancers are confined to the pancreas; some stage 2 cancers have unfold to close by lymph nodes however haven’t unfold to distant websites.

“Now we have established an exosome-based signature that mixes exosomal microRNAs and cell-free DNA to establish sufferers with early-stage pancreatic most cancers robustly,” stated Xu.

“Our method presents a liquid biopsy take a look at superior to CA19-9 measurement alone for early-stage illness,” Goel added. “Furthermore, we evaluated the effectiveness of our assay in a number of completely different populations, together with populations of various ethnic and geographical backgrounds.”

Whereas further analysis is required earlier than this take a look at may be deployed to the final inhabitants, the researchers famous that it would profit sure teams with a excessive threat for pancreatic most cancers, akin to these with continual pancreatitis, new-onset diabetes, or a household historical past of pancreatic cancer.

A limitation of the examine was the restricted variety of Black people included within the examine cohorts. One other limitation was the shortage of a longtime microRNA management towards which to normalize the degrees of candidate microRNAs used to develop the signature.