Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck

Ying Wen Su, Yun Ho Lin, Man Hui Pai, An Chi Lo, Yu Chieh Lee, I. Chih Fang, Johnson Lin, Ruey Kuen Hsieh, Yi Fang Chang, Chi Long Chen

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Background: Epidemiological studies have indicated that impaired glucose metabolism may increase the risk of squamous cell carcinoma of the head and neck (SCCHN). AMP-activated protein kinase (AMPK) regulates glucose and lipid metabolism via the phosphorylation and subsequent inactivation of its downstream target acetyl-CoA carboxylase (ACC).Thus, we analyzed the expression of pAMPK and its downstream target phosphorylated acetyl-CoA carboxylase (pACC), as well as their impact on the survival of patients with resected SCCHN. Methods: One hundred eighteen patients with surgically resected SCCHN were enrolled. Immunohistochemical (IHC) staining for pAMPK and pACC was performed using tissue microarrays of operative specimens of SCCHN. The expression was divided into two or three groups according to the IHC score [pAMPK: negative (0), positive (1-3); pACC: negative (0), low expression (1, 2), and high expression (3)]. Statistical analysis was performed to determine the association of pAMPK expression with clinicopathological features and pACC and pErk expression. Results: The positive rates of pAMPK and pACC expression were 64.4% (76/118) and 68.6% (81/118), respectively. pAMPK was significantly higher in patients aged younger than 60 years (P= 0.024; χ2test) and those with early-stage (T1/T2; P = 0.02; χ2 test) and oral cavity (P = 0.026; Fisher's exact test) tumors. In multivariate analysis, pAMPK expression was not significantly correlated with overall survival (OS) (adjusted hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.35-1.23), whereas high pACC expression was independently associated with worse OS in node-positive patients (adjusted HR: 17.58; 95% CI: 3.50-88.18). Conclusions: Strong expression of pACC was found to be an independent prognostic marker for patients with nodepositive SCCHN. Our results suggest that pACC may play a role in tumor progression of SCCHN and may help to identify patient subgroups at high risk for poor disease outcome.

Original languageEnglish
Article numbere96183
JournalPLoS One
Issue number4
Publication statusPublished - Apr 25 2014


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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