A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women

Abstract

To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case-control targeted metabolomics study using pre-diagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the liquid chromatography-mass spectrometry to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired t-test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference. False discovery rate (FDR) adjusted q-value < 0.25 was indicated statistically significant. Logistic regression model and receiver operating characteristic (ROC) curve analysis were used to evaluate the clinical utility of the metabolites. Among 30 case/control pairs, 1-methyl-L-tryptophan (L-1MT) was significantly lower in the cases than in the controls (log2 FC= - 0.35; q-value = 0.03). The Area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer.