Journal
ANNALS OF ONCOLOGY
Volume 23, Issue 1, Pages 78-85Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdr036
Keywords
AMP-activated protein kinase; LKB1; non-small-cell lung cancer; tobacco smoking
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Funding
- National Institutes of Health [R01 CA109520, CA100816]
- Department of Defense [W81XWH-04-1-0142-01-VITAL]
- National Institutes of Health through MD Anderson's Cancer Center [CA016672]
- NATIONAL CANCER INSTITUTE [P30CA016672, R01CA109520, R01CA100816] Funding Source: NIH RePORTER
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Background: The aim of this study is to investigate the prognostic role of phosphorylated AMP-activated protein kinase (pAMPK) in surgically resected non-small-cell lung cancer (NSCLC). Methods: Immunohistochemical staining of pAMPK was carried out on tissue microarrays containing 463 samples obtained from patients with NSCLC and correlated with clinicopathological characteristics and survival. Results: pAMPK expression levels were significantly higher in never smokers versus former smokers versus current smokers (P = 0.045). A positive pAMPK expression was associated with increased overall survival (OS) and recurrence-free survival (RFS) (P = 0.0009 and P = 0.0007, respectively). OS and RFS were statistically superior in pAMPK-positive than in pAMPK-negative patients with adenocarcinoma (ADC; median OS: 5.6 and 4.2 years, respectively, P = 0.0001; median RFS: 5.0 and 2.4 years, respectively, P = 0.001), whereas they were similar in those patients with squamous cell carcinoma. Multivariate analysis confirmed that pAMPK positivity was associated with OS [hazard ratio (HR) = 0.574, 95% confidence interval (CI) 0.418-0.789, P = 0.0006) and RFS (HR = 0.608, 95% CI 0.459-0.807, and P = 0.0006), independent of clinical covariates. Conclusions: High pAMPK expression levels are associated with increased survival in patients with NSCLC, especially those with ADC. Our results support further evaluation of AMP-activated protein kinase as a potential prognostic and therapeutic target for lung cancer.
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