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. 2019 Oct 30;8(11):1357.
doi: 10.3390/cells8111357.

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  1 , Georg Oberhuber  2   3 , Peter Birner  4 , Michaela Schlederer  5 , Michael Kenn  6 , Wolfgang Schreiner  7 , Gerd Jomrich  8 , Sebastian F Schoppmann  9 , Michael Gnant  8 , William Tse  10   11 , Lukas Kenner  12   13   14   15
Affiliations

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 et al. Cells. .

Erratum in

Abstract

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.

Keywords: AF1Q; MLLT11; STAT; WNT; esophageal cancer; prognosis.

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Conflict of interest statement

M.G. has received institutional research support from AstraZeneca, Roche, Novartis, and Pfizer, and has received lecture fees, honoraria for participation on advisory boards, and travel support from Amgen, AstraZeneca, Celgene, EliLilly, Invectys, Pfizer, Nanostring, Novartis, Roche, and Medison. He has served as a consultant for AstraZeneca and EliLilly, and an immediate family member is employed by Sandoz. None of the other authors have financial and personal relationships with individuals or organizations that could inappropriately influence their work.

Figures

Figure 1
Figure 1
Examples of immunohistochemical (IHC) stained esophageal adenocarcinoma. Examples of AF1q expression in high-risk esophageal adenocarcinoma: Right example showing enhanced AF1q expression in high-risk adenocarcinoma vs. left example showing no AF1q expression in low-risk esophageal adenocarcinoma, size bar 100 µm.
Figure 2
Figure 2
Kaplan–Meier analysis for disease-free survival in esophageal cancer (EC) patients. EC patients with high tumoral AF1q levels relapse earlier compared to patients with low or no tumoral AF1q expression (disease-free survival (DFS), log rank: p = 0.0005).
Figure 3
Figure 3
Kaplan–Meier analysis for disease-specific survival in esophageal cancer (EC) patients. EC patients with high tumoral AF1q die earlier compared to patients with low or no tumoral AF1q expression (disease-specific survival (DSS), log rank; p = 0.003).
See this image and copyright information in PMC

References

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