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Open AccessArticle

The Oncogene AF1Q is Associated with WNT and STAT Signaling and Offers a Novel Independent Prognostic Marker in Patients with Resectable Esophageal Cancer

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Division of General Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
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Institute of Pathology, Department of Experimental and Translational Pathology, Medical University of Vienna, 1090 Vienna, Austria
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PIZ—Patho im Zentrum GmbH, 3100 St. Poelten, Lower Austria, Austria
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Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, 1090 Vienna, Austria
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James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
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Division of Blood and Bone Marrow Transplantation, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
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Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, 1090 Vienna, Austria
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Institute of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
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CBmed Core Lab 2, Medical University of Vienna, 1090 Vienna, Austria
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Authors to whom correspondence should be addressed.
Cells 2019, 8(11), 1357; https://doi.org/10.3390/cells8111357
Received: 4 October 2019 / Revised: 24 October 2019 / Accepted: 29 October 2019 / Published: 30 October 2019
(This article belongs to the Special Issue Killing Cancer: Discovery and Selection of New Target Molecules)
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 EC 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 tissue samples, an elevated expression of AF1q was associated with the expression of 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. Testing AF1q could facilitate prognosis estimation and provide a possibility of identifying the patients responsive to the therapeutic blockade of its oncogenic downstream targets. View Full-Text
Keywords: AF1Q; MLLT11; WNT; STAT; esophageal cancer; prognosis AF1Q; MLLT11; WNT; STAT; esophageal cancer; prognosis
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Gruber, E.S.; Oberhuber, G.; Birner, P.; Schlederer, M.; Kenn, M.; Schreiner, W.; Jomrich, G.; Schoppmann, S.F.; Gnant, M.; Tse, W.; Kenner, L. The Oncogene AF1Q is Associated with WNT and STAT Signaling and Offers a Novel Independent Prognostic Marker in Patients with Resectable Esophageal Cancer. Cells 2019, 8, 1357.

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