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Expression of the receptor tyrosine kinase EphA2 is increased in smokers and predicts poor survival in non-small cell lung cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2009 Jul 01; Vol. 15 (13), pp. 4423-30. Date of Electronic Publication: 2009 Jun 16. - Publication Year :
- 2009
-
Abstract
- Purpose: Up-regulation of the receptor tyrosine kinase EphA2 has been shown in several epithelial cancers. Epidermal growth factor receptor (EGFR) and K-Ras have been reported to regulate EphA2 in several in vitro models, but this regulation has never been examined in tumors from patients. Because of the established importance of EGFR and K-Ras mutations in non-small cell lung cancer (NSCLC), we investigated the relationship between these mutations and EphA2 in this cancer type. The significance of EphA2 expression was further examined by testing for correlation with other clinical parameters.<br />Experimental Design: EphA2 expression was analyzed by immunohistochemistry in tissue microarray format using surgically resected NSCLC specimens (n = 279). EGFR and K-Ras mutation status was determined for most specimens. The correlation between EphA2 expression and EGFR or K-Ras mutation status was examined, along with several clinicopathologic variables of the tumors. The effects of increasing EGFR and K-Ras activity on EphA2 expression and activity were examined in two cell lines.<br />Results: EphA2 expression was detected in >90% of tumor samples. Expression of EphA2 was positively correlated with activated EGFR but not with EGFR mutations. EphA2 expression was increased in patients harboring K-Ras mutations. EphA2 expression was positively correlated with a history of smoking, and high EphA2 scores predicted poorer progression-free and overall survivals.<br />Conclusions: EphA2 expression in NSCLC is associated with K-Ras mutations, EGFR activation, smoking history, and poor prognosis. EphA2 expression is up-regulated in the context of EGFR or K-Ras activation. The potential of EphA2 as a therapeutic target for NSCLC should be further investigated.
- Subjects :
- Carcinoma, Non-Small-Cell Lung diagnosis
Carcinoma, Non-Small-Cell Lung epidemiology
Cell Line, Tumor
ErbB Receptors metabolism
ErbB Receptors physiology
Female
Gene Expression Regulation, Neoplastic
Genes, ras physiology
Humans
Lung Neoplasms diagnosis
Lung Neoplasms epidemiology
Male
Mutant Proteins physiology
Prognosis
Receptor, EphA2 metabolism
Smoking adverse effects
Smoking epidemiology
Survival Analysis
Up-Regulation genetics
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung mortality
Lung Neoplasms genetics
Lung Neoplasms mortality
Receptor, EphA2 genetics
Smoking genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 15
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 19531623
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-09-0473