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EGR1 Predicts PTEN and Survival in Patients With Non–Small-Cell Lung Cancer

From the Thoracic Oncology Program and Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute; and Departments of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, FL

Address reprint requests to Eric B. Haura, MD, Thoracic Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, MRC3 E, Room 3056, 12902 Magnolia Dr, Tampa, FL 33612-9497; e-mail: hauraeb{at}moffitt.usf.edu

PURPOSE: The zinc finger transcription factor early growth response gene 1 (EGR1) is underexpressed in non–small-cell lung cancer (NSCLC) compared with normal lung. EGR1 expression has been linked to tumor suppression as a result of cell cycle arrest and apoptosis through regulation of tumor suppressor pathways including PTEN. For these reasons, we hypothesized that reduced levels of EGR1 would correlate with inferior outcome in patients with NSCLC.

PATIENTS AND METHODS: Patients who underwent surgical resection for NSCLC had RNA extracted from tumor tissue and EGR1 gene expression was quantified by real-time quantitative polymerase chain reaction. The levels of EGR1 expression were examined in relationship to patient characteristics, histology, tumor stage, PTEN expression, and overall and disease-free survival.

RESULTS: EGR1 expression strongly correlated with PTEN expression (P < .0001). No correlation of EGR1 with histology or stage was detected. Patients with high levels of EGR1 had better overall and disease-free survival compared with patients with low levels of EGR1 (P = .040 and P = .096, respectively). In a stratified log-rank test, low EGR1 expression was predictive of poor survival independent of tumor stage.

CONCLUSION: EGR1 gene expression predicts PTEN levels and survival after surgical resection of NSCLC. Consistent with its known tumor suppressor properties, lower levels of EGR1 are associated with poor outcome. Identification of patients with low EGR1 therefore may identify patients at high risk for disease recurrence and may also identify patients who have tumors resistant to therapy secondary to loss of pathways such as PTEN.

Supported in part by NIH grants R01 CA 102726, NIH U01 CA101222, and by the Molecular Biology Core Facility and the Molecular Imaging Core at the H. Lee Moffitt Cancer Center & Research Institute.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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