Mesoporous Magnetic Graphene for Serum Metabolic Profiling in Non-Invasive Early Detection and Diagnosis of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal cancer, typically diagnosed at advanced stages due to its asymptomatic onset and challenges in early detection. To address the critical need for the early diagnosis of PDAC, we developed a laser desorption/ionization mass spectrometry (LDI-MS) platform based on mesoporous silica-modified magnetic graphene (MG@mSiO₂). MG@mSiO₂ exhibited exceptional ultraviolet (UV) absorption, efficient ionization, and minimal background interference, enabling high-resolution profiling of serum metabolic fingerprints (SMFs). Based on the extracted SMFs, we constructed a Random Forest (RF) model to classify PDAC patients, high-risk (HR) individuals, and healthy controls (HC), achieving an accuracy of 97.5% in the independent test set. Additionally, a six-metabolite biomarker panel was identified, showing strong diagnostic potential with sensitivity and accuracy exceeding 89.1% for distinguishing HC from PDAC. When coupled with the serological marker carbohydrate antigen 19-9 (CA19-9), the integrated strategy delivered significantly improved diagnostic performance, achieving high accuracy ranging from 95.3% to 100% in distinguishing HR and PDAC patients from HC. Furthermore, metabolic pathway analysis revealed key pathways associated with PDAC progression, providing mechanistic insights into the disease. This work provides a powerful diagnostic tool for PDAC screening, establishing a foundation for early detection and precision medicine in clinical practice.