RRC ID 52198
Author Seike M, Kim CH, Zou F, Noro R, Chiba M, Ishikawa A, Κunugi S, Kubota K, Gemma A.
Title AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier.
Journal Oncol. Rep.
Abstract AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD. Protein expression was also assayed using western blot analysis in 10 lung AD cell lines. AXL-positive (AXL+), GAS6-positive (GAS6+), or AXL+/GAS6+ staining was significantly associated with vimentin-positive (vimentin+) expression. AXL+/GAS6+ and vimentin+ showed a negative tendency toward an association with EGFR mutation. AXL+, GAS6+, or AXL+/GAS6+ status significantly correlated with poor overall survival. In stage I cases, AXL+/GAS6+ status significantly correlated with poor overall survival and disease-free survival, especially in cases with wild-type EGFR. In multivariate analysis, AXL/GAS6 classifications in stage I as well as in stages I-III lung AD were found to be independent factors for poor patient outcomes. Unlike lung AD cell lines with mutant EGFR, almost all cells with wild-type EGFR showed AXL and vimentin co-expression as determined by western blotting. AXL+ and GAS6+ expression is relevant to a poor prognosis in resected lung AD patients at stage I. AXL/GAS6 might serve as crucial predictive and prognostic biomarkers and targets to identify individuals at high risk of post-operative death.
Volume 37(6)
Pages 3261-3269
Published 2017-6
DOI 10.3892/or.2017.5594
PMID 28440492
MeSH Adenocarcinoma / drug therapy* Adenocarcinoma / genetics Adenocarcinoma / pathology Adenocarcinoma of Lung Aged Biomarkers, Tumor / genetics* Cell Line, Tumor Disease-Free Survival Drug Resistance, Neoplasm / genetics ErbB Receptors / antagonists & inhibitors ErbB Receptors / genetics Female Gene Expression Regulation, Neoplastic Humans Intercellular Signaling Peptides and Proteins / genetics* Lung Neoplasms / drug therapy* Lung Neoplasms / genetics Lung Neoplasms / pathology Male Middle Aged Neoplasm Staging Prognosis Protein Kinase Inhibitors / administration & dosage Proto-Oncogene Proteins / genetics* Receptor Protein-Tyrosine Kinases / genetics*
IF 3.041
Human and Animal Cells LC-2/ad(RCB0440) PC-9(RCB4455)