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

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

doi:10.3892/ol.2018.8795

August-2018 Volume 16 Issue 2

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August-2018 Volume 16 Issue 2

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Article

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

Authors:
- 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
View Affiliations / Copyright

Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565‑0871, Japan, Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565‑0871, Japan, Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka 565‑0871, Japan
Pages: 1827-1834
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Published online on: May 24, 2018

https://doi.org/10.3892/ol.2018.8795
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Abstract

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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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