The expression levels of one-
carbon metabolic
enzymes were investigated and observed to be correlated with clinicopathological parameters in patients with
pancreatic cancer. Mitochondrial one-
carbon metabolism comprises a network of biological reactions that integrate nutrient status with
nucleotide synthesis,
amino acid metabolism,
antioxidant reduced
nicotinamide adenine dinucleotide phosphate production and epigenetic methylation processes. Previous studies have reported that the hyper-activation of mitochondrial one-
carbon metabolism serves a significant role in malignant
cancer phenotypes. A total of 103 patients underwent surgical resection of pancreatic ductal
adenocarcinomas (PDAC) at Osaka University Hospital between April 2007 and December 2013 and were enrolled in this study. Subsequently, the expression of the one-
carbon metabolic
enzymes methylenetetrahydrofolate dehydrogenase 2 (MTHFD2),
aldehyde dehydrogenase 1 family member L2 (ALDH1L2), and
serine hydroxymethyltransferase (SHMT2) was examined using immunohistochemical analysis. The immunohistochemical analyses demonstrated that patients with high expression levels of MTHFD2, ALDH1L2 or SHMT2 had significantly poor overall survival (OS) and disease-free survival (DFS) rates, as compared with patients with low expression levels. Furthermore, multivariate Cox proportional hazards analysis indicated that MTHFD2 and ALDH1L2 were independent prognostic factors for OS and DFS, whereas SHMT2 was not predictive of DFS. However, high and low expression levels of all three
folate metabolic
enzymes were significantly associated with improved OS and DFS, compared with the high expression of one or two
folate metabolic
enzymes. The expression levels of mitochondrial one-
carbon metabolic
enzymes are independent prognostic factors and potential therapeutic targets for future
pancreatic cancer treatments.