W N William1, J-S Kim1, D D Liu2, L Solis3, C Behrens1, J J Lee2, S M Lippman1, E S Kim1, W K Hong1, I I Wistuba4, H-Y Lee5. 1. Departments of Thoracic/Head & Neck Medical Oncology. 2. Departments of Biostatistics. 3. Departments of Biostatistics Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. 4. Departments of Thoracic/Head & Neck Medical Oncology; Departments of Biostatistics Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. 5. Departments of Thoracic/Head & Neck Medical Oncology; Departments of College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: hylee135@snu.ac.kr.
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.
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.
Authors: Kathryn A Gold; Edward S Kim; Diane D Liu; Ping Yuan; Carmen Behrens; Luisa M Solis; Humam Kadara; David C Rice; Ignacio I Wistuba; Stephen G Swisher; Wayne L Hofstetter; J Jack Lee; Waun K Hong Journal: Clin Cancer Res Date: 2013-12-23 Impact factor: 12.531
Authors: Ni Zhao; Matthew D Wilkerson; Usman Shah; Xiaoying Yin; Anyou Wang; Michele C Hayward; Patrick Roberts; Carrie B Lee; Alden M Parsons; Leigh B Thorne; Benjamin E Haithcock; Juneko E Grilley-Olson; Thomas E Stinchcombe; William K Funkhouser; Kwok-Kin Wong; Norman E Sharpless; D Neil Hayes Journal: Lung Cancer Date: 2014-08-30 Impact factor: 5.705