The Oncogene AF1Q is Associated with WNT and STAT Signaling and Offers a Novel Independent Prognostic Marker in Patients with Resectable Esophageal Cancer
Elisabeth S. Gruber,
Georg Oberhuber,
Peter Birner,
Michaela Schlederer,
Michael Kenn,
Wolfgang Schreiner,
Gerd Jomrich,
Sebastian F. Schoppmann,
Michael Gnant,
William Tse,
Lukas Kenner
Affiliations
Elisabeth S. Gruber
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
Georg Oberhuber
Institute of Pathology, Department of Experimental and Translational Pathology, Medical University of Vienna, 1090 Vienna, Austria
Peter Birner
Institute of Pathology, Department of Experimental and Translational Pathology, Medical University of Vienna, 1090 Vienna, Austria
Michaela Schlederer
Institute of Pathology, Department of Experimental and Translational Pathology, Medical University of Vienna, 1090 Vienna, Austria
Michael Kenn
Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, 1090 Vienna, Austria
Wolfgang Schreiner
Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, 1090 Vienna, Austria
Gerd Jomrich
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
Sebastian F. Schoppmann
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
Michael Gnant
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
William Tse
James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
Lukas Kenner
Institute of Pathology, Department of Experimental and Translational Pathology, Medical University of Vienna, 1090 Vienna, Austria
: AF1q impairs survival in hematologic and solid malignancies. AF1q expression is associated with tumor progression, migration, and chemoresistance, and acts as a transcriptional co-activator in WNT and STAT signaling. This study evaluates the role of AF1q in patients with resectable esophageal cancer (EC). A total of 278 patients operated on for esophageal cancer were retrospectively included, and the expression of AF1q, CD44, and pYSTAT3 was analyzed following immunostaining. Quantified data were processed to correlational and survival analysis. In EC patients, an elevated expression of AF1q was associated with CD44 (p = 0.004), and pYSTAT3 (p = 0.0002). High AF1q expression in primary tumors showed high AF1q expression in the corresponding lymph nodes (p = 0.016). AF1q expression was higher after neoadjuvant therapy (p = 0.0002). Patients with AF1q-positive EC relapsed and died earlier compared to patients with AF1q-negative EC (disease-free survival (DFS), p = 0.0005; disease-specific survival (DSS), p = 0.003); in the multivariable Cox regression model, AF1q proved to be an independent prognostic marker (DFS, p = 0.01; DSS, p = 0.03). AF1q is associated with WNT and STAT signaling; it impairs and independently predicts DFS and DSS in patients with resectable EC. The testing of AF1q could facilitate prognosis estimation and provide a possibility of identifying the patients responsive to the therapeutic blockade of its oncogenic downstream targets.
