Metabolomics Identifies Biomarker Signatures to Differentiate Pancreatic Cancer from Type 2 Diabetes Mellitus in Early Diagnosis

Abstract

Background and Purpose. Carbohydrate antigen 19-9 (CA19-9) based approaches differentiate less than 60% of cases of pancreatic cancer (PC) from those of pancreatic tissue damage caused by chronic pancreatitis and type 2 diabetes mellitus (DM). This study aims to identify potential blood-derived candidate biomarkers for improved diagnosis sensitivity. Methods. Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. Results. We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. Conclusion. We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.