PMID- 30008872 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 16 IP - 2 DP - 2018 Aug TI - The mitochondrial one-carbon metabolic pathway is associated with patient survival in pancreatic cancer. PG - 1827-1834 LID - 10.3892/ol.2018.8795 [doi] AB - 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. FAU - Noguchi, Kozo AU - Noguchi K AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Konno, Masamitsu AU - Konno M AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Koseki, Jun AU - Koseki J AD - Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Nishida, Naohiro AU - Nishida N AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Kawamoto, Koichi AU - Kawamoto K AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Yamada, Daisaku AU - Yamada D AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Asaoka, Tadafumi AU - Asaoka T AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Noda, Takehiro AU - Noda T AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Wada, Hiroshi AU - Wada H AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Gotoh, Kunihito AU - Gotoh K AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Sakai, Daisuke AU - Sakai D AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Kudo, Toshihiro AU - Kudo T AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Satoh, Taroh AU - Satoh T AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Eguchi, Hidetoshi AU - Eguchi H AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Doki, Yuichiro AU - Doki Y AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Mori, Masaki AU - Mori M AD - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. FAU - Ishii, Hideshi AU - Ishii H AD - Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. AD - Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. LA - eng PT - Journal Article DEP - 20180524 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC6036444 OTO - NOTNLM OT - ALDH1L2 OT - MTHFD2 OT - SHMT2 OT - folate pathway OT - one-carbon metabolism OT - pancreatic cancer EDAT- 2018/07/17 06:00 MHDA- 2018/07/17 06:01 PMCR- 2018/05/24 CRDT- 2018/07/17 06:00 PHST- 2016/02/24 00:00 [received] PHST- 2017/03/17 00:00 [accepted] PHST- 2018/07/17 06:00 [entrez] PHST- 2018/07/17 06:00 [pubmed] PHST- 2018/07/17 06:01 [medline] PHST- 2018/05/24 00:00 [pmc-release] AID - OL-0-0-8795 [pii] AID - 10.3892/ol.2018.8795 [doi] PST - ppublish SO - Oncol Lett. 2018 Aug;16(2):1827-1834. doi: 10.3892/ol.2018.8795. Epub 2018 May 24.