Association between phosphorylated AMP-activated protein kinase and MAPK3/1 expression and prognosis for patients with gastric cancer

Oncology. 2013;85(2):78-85. doi: 10.1159/000351234. Epub 2013 Jul 16.

Abstract

Objectives: Phosphorylated AMP-activated protein kinase (pAMPK) plays a central role in cellular metabolic sensing and energy balance homeostasis, and interacts with various pathways [e.g., TP53, mTOR, NUAK2 (sucrose nonfermenting-like kinase), MAPK3/1 (ERK) and PDK]. Therefore, the present study analyzed the expression of pAMPK, NUAK2, MAPK3/1 and PDK-1 and their effect on the survival of patients with resected gastric cancer.

Methods: A total of 621 patients with gastric adenocarcinoma surgically resected with curative intent were enrolled in the study. Immunohistochemical staining for pAMPK, NUAK2, MAPK3/1 and PDK-1 was performed using tissue microarrays of surgical specimens of gastric cancer tissue.

Results: Positive pAMPK, NUAK2, MAPK3/1 and PDK-1 expression was observed in 379 (61.0%), 257 (41.4%), 327 (52.7%) and 67 (10.8%) cases, respectively. Multivariate survival analysis showed a significantly better survival for the patients with positive pAMPK or MAPK3/1 expression than for the patients with a negative expression [pAMPK: disease-free survival (DFS), hazard ratio (HR) = 0.750, 95% confidence interval (CI) = 0.568-0.970, p = 0.030; MAPK3/1: DFS, HR = 0.692, 95% CI = 0.720-0.974, p = 0.021), while NUAK2 or PDK-1 expression had no effect on survival.

Conclusion: pAMPK or MAPK3/1 expression was found to be an independent prognostic marker for patients with resected gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adenocarcinoma / blood
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoembryonic Antigen / blood
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Multivariate Analysis
  • Phosphorylation
  • Prognosis
  • Proportional Hazards Models
  • Protein Processing, Post-Translational*
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / mortality
  • Young Adult

Substances

  • Carcinoembryonic Antigen
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • NUAK2 protein, human
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • AMP-Activated Protein Kinases