AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

  • Authors:
    • Masahiro Seike
    • Cheol-Hong Kim
    • Fenfei Zou
    • Rintaro Noro
    • Mika Chiba
    • Arimi Ishikawa
    • Shinobu Κunugi
    • Kaoru Kubota
    • Akihiko Gemma
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  • Published online on: April 21, 2017     https://doi.org/10.3892/or.2017.5594
  • Pages: 3261-3269
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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.
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June-2017
Volume 37 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Seike M, Kim C, Zou F, Noro R, Chiba M, Ishikawa A, Κunugi S, Kubota K and Gemma A: AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier. Oncol Rep 37: 3261-3269, 2017
APA
Seike, M., Kim, C., Zou, F., Noro, R., Chiba, M., Ishikawa, A. ... Gemma, A. (2017). AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier. Oncology Reports, 37, 3261-3269. https://doi.org/10.3892/or.2017.5594
MLA
Seike, M., Kim, C., Zou, F., Noro, R., Chiba, M., Ishikawa, A., Κunugi, S., Kubota, K., Gemma, A."AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier". Oncology Reports 37.6 (2017): 3261-3269.
Chicago
Seike, M., Kim, C., Zou, F., Noro, R., Chiba, M., Ishikawa, A., Κunugi, S., Kubota, K., Gemma, A."AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier". Oncology Reports 37, no. 6 (2017): 3261-3269. https://doi.org/10.3892/or.2017.5594