The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma
Journal
Oncotarget
Journal Volume
7
Journal Issue
24
Pages
36956-36970
Date Issued
2016
Author(s)
Abstract
Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P < 0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients.
SDGs
Other Subjects
antineoplastic agent; AXL protein; epidermal growth factor receptor 2; foretinib; lapatinib; protein tyrosine kinase; unclassified drug; anilide; antineoplastic agent; axl receptor tyrosine kinase; epidermal growth factor receptor 2; ERBB2 protein, human; foretinib; oncoprotein; protein tyrosine kinase; quinoline derivative; tumor marker; adult; adverse outcome; Article; cancer diagnosis; cancer growth; cancer mortality; cancer patient; cancer prognosis; cancer resistance; carcinoma cell; chemosensitivity; controlled study; distant metastasis; drug efficacy; drug potentiation; drug targeting; esophageal squamous cell carcinoma; esophageal tissue; female; high risk patient; human; human cell; human tissue; immunohistochemistry; major clinical study; male; outcome assessment; primary tumor; protein expression; aged; disease free survival; drug effects; drug resistance; esophagus tumor; Kaplan Meier method; metabolism; middle aged; mortality; pathology; prognosis; squamous cell carcinoma; tumor cell line; tumor invasion; Adult; Aged; Anilides; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Line, Tumor; Disease-Free Survival; Drug Resistance, Neoplasm; Esophageal Neoplasms; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Proto-Oncogene Proteins; Quinolines; Receptor Protein-Tyrosine Kinases; Receptor, ErbB-2
Publisher
Impact Journals LLC
Type
journal article