Association between Phosphorylated AMP-Activated Protein Kinase and MAPK3/1 Expression and Prognosis for Patients with Gastric Cancer

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.