A study published in Science Advances reports the identification of protein signatures in circulating extracellular vesicles that may help detect pancreatic ductal adenocarcinoma (PDAC) at earlier stages. The work highlights the potential of blood-based diagnostics in a cancer type that is often diagnosed only after progression to advanced disease.
Researchers analyzed extracellular vesicles (EVs) isolated from blood samples of patients with PDAC, individuals with chronic pancreatitis, and healthy participants. Using a proteomics-based workflow, they profiled more than 4,000 unique proteins carried within or on the surface of EVs. Statistical analysis of the protein patterns revealed distinct combinations associated with pancreatic cancer.
Among the proteins identified, integrin αV (ITGAV) and ephrin type-A receptor 2 (EPHA2) were found to be consistently enriched in vesicles from patients with PDAC. When tested in an independent validation group, these proteins, along with other components of the biomarker panel, distinguished early PDAC from chronic pancreatitis and healthy controls with greater sensitivity and specificity than carbohydrate antigen 19-9 (CA19-9), the most commonly used serum marker for pancreatic cancer.
CA19-9 is currently the only clinically validated biomarker for pancreatic cancer but has well-documented limitations. It is elevated in many benign conditions, including inflammatory pancreatic disease, and is not expressed in all patients with pancreatic cancer. The EV-based biomarker panel described in this study showed improved performance across different patient subsets, suggesting it could reduce both false positives and false negatives.
The study also illustrates how EV proteomics might complement existing diagnostic methods. The workflow described – ultracentrifugation to isolate vesicles followed by mass spectrometry to analyze protein cargo – relies on technologies already familiar in research and clinical laboratories. If validated further, such methods may be integrated into diagnostic pathways to provide earlier, less invasive detection of pancreatic cancer.
The authors note that further studies will be needed to evaluate reproducibility across laboratories, standardize EV isolation and analysis platforms, and test the biomarker panel in larger, prospective cohorts. They also emphasize that the findings do not replace imaging, cytology, or tissue-based diagnostics but could add value as part of a multimodal approach.
Overall, the study offers evidence that circulating vesicle-derived proteins, particularly ITGAV and EPHA2, may serve as markers for early pancreatic cancer detection. For pathologists and laboratory professionals, these results reflect the growing role of liquid biopsy and proteomic profiling in cancer diagnostics and the potential for improved accuracy in distinguishing malignant from benign pancreatic disease.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
