Untargeted metabolomics characterization of the resectable pancreatic ductal adenocarcinoma

BACKGROUND: Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to the lack of specific symptoms and screening methods. Only less than 10% of PDAC patients are candidates for surgery at the time of diagnosis. Thus, there is a great global unmet need for valuable biomarkers that could improve the opportunity to detect PDAC at the resectable stage. This study aimed to develop a potential biomarker model for the detection of resectable PDAC by tissue and serum metabolomics. METHODS: Ultra-high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was performed for metabolome quantification in 98 serum samples (49 PDAC patients and 49 healthy controls (HCs)) and 20 pairs of matched pancreatic cancer tissues (PCTs) and adjacent noncancerous tissues (ANTs) from PDAC patients. Univariate and multivariate analyses were used to profile the differential metabolites between PDAC and HC. RESULTS: A total of 12 differential metabolites were present in both serum and tissue samples of PDAC. Among them, a total of eight differential metabolites showed the same expressional levels, including four upregulated and four downregulated metabolites. Finally, a panel of three metabolites including 16-hydroxypalmitic acid, phenylalanine, and norleucine was constructed by logistic regression analysis. Notably, the panel was capable of distinguishing resectable PDAC from HC with an AUC value of 0.942. Additionally, a multimarker model based on the 3-metabolites-based panel and CA19-9 showed a better performance than the metabolites panel or CA19-9 alone (AUC: 0.968 vs. 0.942, 0.850). CONCLUSIONS: Taken together, the resectable early-stage PDAC has unique metabolic features in serum and tissue samples. The defined panel of three metabolites has the potential value for early screening of PDAC at the resectable stage.