Abstract
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response to chemotherapy, aggressive tumor biology, and high rates of tumor recurrence. Therefore, the development of a non-invasive and effective method for early detection of PDAC is crucial to improving patient outcomes. Continued research and exploration in this area are essential to enhance early detection methods and ultimately improve the prognosis for individuals with PDAC. In this study, we examined 37 exosomal surface proteins through a multiplex flow cytometry test on peripheral plasma samples from a group of 51 clinical control individuals (including healthy volunteers and non-cancer patients (Cholecystectomy, Hernia, healthy volunteers)), 21 pancreatitis, and 48 patients diagnosed with PDAC. Our research findings revealed that the level of exosomal CD40 expression is significantly lower in patients with PDAC and pancreatitis compared to non-cancer patients (p < 0.0001). Additionally, pancreatitis patients exhibited higher levels of exosomal CD25 expression than PDAC patients (p = 0.0104). PDAC patients with higher exo-CD40 had worse survival than patients with lower exo-CD40 (p = 0.0035). Similarly, PDAC patients with higher exo-CD25 showed worse survival in comparison to patients with lower exo-CD25 (p = 0.04). Statistical analysis revealed that exosomal CD40 achieved an AUC of 0.827 in distinguishing PDAC from clinical controls. Combining exo-CD40 along with exo-CD25 and CA19-9 discriminated PDAC patients from clinical controls with an AUC of 0.92. Exo-CD40 and exo-CD25 proteins found in exosomes isolated from plasma can serve as excellent non-invasive biomarkers for the early diagnosis of PDAC. Further larger scale studies are needed to validate combined exo-CD40 and exo-CD25 as a diagnostic tool for the identification of PDAC patients through non-invasive liquid biopsy.