Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer

Oncology. 2015;89(6):351-9. doi: 10.1159/000439571. Epub 2015 Oct 7.

Abstract

Purpose: Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications.

Methods: From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive.

Results: During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis.

Conclusions: In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Colon / enzymology
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Phosphoglycerate Dehydrogenase / metabolism*
  • Prognosis
  • Protein-Serine-Threonine Kinases / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Serine / metabolism*
  • Survival Rate
  • Tissue Array Analysis
  • Transaminases / metabolism*

Substances

  • Biomarkers, Tumor
  • PDK1 protein, human
  • PDK2 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Serine
  • Phosphoglycerate Dehydrogenase
  • Transaminases
  • phosphoserine aminotransferase
  • Protein-Serine-Threonine Kinases