Multiplexed Quantitation of Plasma Proteins by Targeted Mass Spectrometry for Early Diagnosis of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PC) is the sixth leading cause of cancer-related deaths worldwide. Patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of PC, have a 5-year survival rate of approximately 10%. This low survival rate is mainly attributed to late-stage diagnoses and the lack of robust screening methods. Several serum proteins have been proposed as potential PDAC biomarkers, but they have not been introduced into clinical practice due to their low sensitivity and specificity. Therefore, the identification of new PDAC biomarkers remains highly important, and multiple reaction monitoring (MRM), a highly accurate mass spectrometry (MS) technique, can be used for this purpose. Using MRM MS analysis, we estimated the concentrations of 103 proteins in peripheral blood plasma from 132 participants: patients with newly diagnosed PDAC at different stages and healthy individuals. We identified six proteins that were differentially presented between healthy controls and patients with PDAC at all stages (adjusted <i>p</i>-value < 0.01), and that were associated with survival rates for 23 months. A developed cross-validated model based on these six proteins showed an average accuracy of 90% in distinguishing between early-stage PDAC and healthy controls (AUC = 0.933). However, further research is needed to implement this model in clinical practice.