Tumor tissue and plasma levels of AXL and GAS6 before and after tyrosine kinase inhibitor treatment in EGFR-mutated non-small cell lung cancer.

Abstract

BACKGROUND:

Non-small cell lung cancer (NSCLC) positive for activating mutations of the epidermal growth factor receptor (EGFR) gene is initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) but eventually develops resistance to these drugs. Upregulation of the receptor tyrosine kinase AXL in tumor tissue has been detected in about one-fifth of NSCLC patients with acquired resistance to EGFR-TKIs. However, the clinical relevance of the levels of AXL and its ligand GAS6 in plasma remains unknown.

METHODS:

Tumor tissue and plasma specimens were collected from 25 EGFR-mutated NSCLC patients before EGFR-TKI treatment or after treatment failure. The levels of AXL and of GAS6 mRNA in tumor tissue were evaluated by immunohistochemistry and chromogenic in situ hybridization, respectively. The plasma concentrations of AXL and GAS6 were measured with enzyme-linked immunosorbent assays.

RESULTS:

AXL expression was detected in three of 12 (25%) and nine of 19 (47%) tumor specimens obtained before and after EGFR-TKI treatment, respectively. All tumor specimens assayed were positive for GAS6 mRNA. The median values for the plasma AXL concentration before and after EGFR TKI treatment were 1 635 and 1 460 pg/mL, respectively, and those for the plasma GAS6 concentration were 4 615 and 6 390 pg./mL, respectively. There was no significant correlation between the plasma levels of AXL or GAS6 and the corresponding expression levels in tumor tissue.

CONCLUSION:

Plasma concentrations of AXL and GAS6 do not reflect tumor expression levels, and their measurement is thus not a viable alternative to direct analysis of tumor tissue in EGFR-mutated NSCLC.

• Authors: Yoshikane Nonagase, Masayuki Takeda, Koichi Azuma, Hidetoshi Hayashi, Koji Haratani, Kaoru Tanaka, Kimio Yonesaka, Hidenobu Ishii, Tomoaki Hoshino, Kazuhiko Nakagawa
• Journal: Thoracic cancer (Thorac Cancer) Vol. 10 Issue 10 Pg. 1928-1935 (10 2019) ISSN: 1759-7714 [Electronic] Singapore
• PMID: 31419057 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chemical References

• Biomarkers, Tumor
• Intercellular Signaling Peptides and Proteins
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins
• growth arrest-specific protein 6
• EGFR protein, human
• ErbB Receptors
• Receptor Protein-Tyrosine Kinases
• Axl Receptor Tyrosine Kinase
• AXL protein, human

Topics

• Aged
• Biomarkers, Tumor
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, metabolism, mortality)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• ErbB Receptors (genetics)
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins (blood, metabolism)
• Liquid Biopsy
• Lung Neoplasms (drug therapy, genetics, metabolism, mortality)
• Male
• Middle Aged
• Mutation
• Prognosis
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Proto-Oncogene Proteins (blood, metabolism)
• Receptor Protein-Tyrosine Kinases (blood, metabolism)
• Axl Receptor Tyrosine Kinase