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.
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; χ2 test) 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 node-positive 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.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Ying-Wen
YW
Su
Division of Oral Pathology, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan.
Yun-Ho
YH
Lin
Department of Anatomy, Taipei Medical University, Taipei, Taiwan.
Man-Hui
MH
Pai
Good Clinical Research Center, Mackay Memorial Hospital, Taipei, Taiwan.
An-Chi
AC
Lo
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
Yu-Chieh
YC
Lee
Good Clinical Research Center, Mackay Memorial Hospital, Taipei, Taiwan.
I-Chih
IC
Fang
Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Johnson
J
Lin
Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Ruey-Kuen
RK
Hsieh
Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Good Clinical Research Center, Mackay Memorial Hospital, Taipei, Taiwan.
Yi-Fang
YF
Chang
Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Chi-Long
CL
Chen
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011499:Protein Processing, Post-Translational; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases; D000263:Adenylate Kinase; D000103:Acetyl-CoA Carboxylase