The mitochondrial one-carbon metabolic pathway is associated with patient survival in pancreatic cancer

Kozo Noguchi, Masamitsu Konno, Jun Koseki, Naohiro Nishida, Koichi Kawamoto, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


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 methy-lenetetrahydrofolate 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.

Original languageEnglish
Pages (from-to)1827-1834
Number of pages8
JournalOncology Letters
Issue number2
Publication statusPublished - Aug 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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