1. The impact of phosphorylated AMP-activated protein kinase expression on lung cancer survival
- Author
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J. Jack Lee, Waun Ki Hong, Luisa M. Solis, Scott M. Lippman, Edward S. Kim, Carmen Behrens, J.-S. Kim, I. I. Wistuba, William N. William, Hui-Young Lee, and Diane Liu
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Kaplan-Meier Estimate ,AMP-Activated Protein Kinases ,Disease-Free Survival ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Phosphorylation ,Protein kinase A ,Lung cancer ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Tissue microarray ,business.industry ,Proportional hazards model ,Hazard ratio ,Original Articles ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Confidence interval ,respiratory tract diseases ,Tissue Array Analysis ,Adenocarcinoma ,Female ,business - Abstract
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.
- Published
- 2012