The importance of mitochondrial folate enzymes in human colorectal cancer

  • Authors:
    • Masaaki Miyo
    • Masamitsu Konno
    • Hugh Colvin
    • Naohiro Nishida
    • Jun Koseki
    • Koichi Kawamoto
    • Kenta Tsunekuni
    • Junichi Nishimura
    • Taishi Hata
    • Ichiro Takemasa
    • Tsunekazu Mizushima
    • Yuichiro Doki
    • Masaki Mori
    • Hideshi Ishii
  • View Affiliations

  • Published online on: November 22, 2016     https://doi.org/10.3892/or.2016.5264
  • Pages: 417-425
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Abstract

Folate plays a pivotal role in the one-carbon metabolism needed for methylation reactions, nucleotide synthesis, and DNA repair. Although folate metabolism was recently shown to be associated with carcinogenesis in some solid tumors, the importance of folate metabolism in colorectal cancer remains unclear. In the present investigation we found that expression of three mitochondrial folate metabolic enzymes, serine hydroxymethyl transferase (SHMT2), methylenetetrahydrofolate dehydrogenase (MTHFD2) and aldehyde dehydrogenase 1 family member L2 (ALDH1L2), were upregulated in human colorectal tumor tissues compared to normal tissues. Colorectal cancer tissue samples were obtained from 117 consecutive patients. We evaluated the expression of the enzymes with immunohistochemical analysis and determined their relevance to clinicopathological characteristics and prognosis. Rates of recurrence-free survival (RFS) and overall survival (OS) in patients with high expression of SHMT2, MTHFD2 and ALDH1L2 tended to be lower than in patients with low expression of SHMT2, MTHFD2 and ALDH1L2 (P=0.446 and P=0.337, P=0.099 and P=0.064, P=0.178 and P=0.257, respectively). Notably, the combined high expression of SHMT2, MTHFD2 and ALDH1L2 (triple high) was more highly associated with poor prognosis than the individual expression levels (RFS; P=0.004 and OS; P=0.037). A multivariate analysis showed that triple high expression was independently associated with RFS (P=0.017). These findings suggested that mitochondrial folate metabolic enzymes could provide a potential therapeutic strategy for treating colorectal cancer.
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January-2017
Volume 37 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Miyo M, Konno M, Colvin H, Nishida N, Koseki J, Kawamoto K, Tsunekuni K, Nishimura J, Hata T, Takemasa I, Takemasa I, et al: The importance of mitochondrial folate enzymes in human colorectal cancer. Oncol Rep 37: 417-425, 2017
APA
Miyo, M., Konno, M., Colvin, H., Nishida, N., Koseki, J., Kawamoto, K. ... Ishii, H. (2017). The importance of mitochondrial folate enzymes in human colorectal cancer. Oncology Reports, 37, 417-425. https://doi.org/10.3892/or.2016.5264
MLA
Miyo, M., Konno, M., Colvin, H., Nishida, N., Koseki, J., Kawamoto, K., Tsunekuni, K., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Doki, Y., Mori, M., Ishii, H."The importance of mitochondrial folate enzymes in human colorectal cancer". Oncology Reports 37.1 (2017): 417-425.
Chicago
Miyo, M., Konno, M., Colvin, H., Nishida, N., Koseki, J., Kawamoto, K., Tsunekuni, K., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Doki, Y., Mori, M., Ishii, H."The importance of mitochondrial folate enzymes in human colorectal cancer". Oncology Reports 37, no. 1 (2017): 417-425. https://doi.org/10.3892/or.2016.5264