A link between RelB expression and tumor progression in laryngeal cancer
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Ioanna Giopanou1, Ioannis Lilis1, Helen Papadaki2, Theodoros Papadas3,* and Georgios T. Stathopoulos1,4,*
1Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece
2Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece
3Department of Otorhinolaryngology & Head and Neck Surgery, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece
4Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University and Helmholtz ZentrumMünchen, Member of The German Center for Lung Research (DZL), Munich, Bavaria 81377, Germany
*Equal senior authors
Georgios T. Stathopoulos, email: email@example.com
Ioanna Giopanou, email: firstname.lastname@example.org
Keywords: head and neck squamous cell carcinoma; nuclear factor (NF)-κB; biomarker; immunohistochemistry; prognosis
Received: May 10, 2017 Accepted: July 25, 2017 Published: December 09, 2017
Laryngeal cancer is a frequent malignancy originating from the squamous vocal epithelium in a multi-stage fashion in response to environmental carcinogens. Although most cases can be cured by surgery and/or radiotherapy, advanced and relapsing disease is common, and biomarkers of such dismal cases are urgently needed. The cancer genome of laryngeal cancers was recently shown to feature a signature of aberrant nuclear factor (NF)-κB activation, but this finding has not been clinically exploited. We analyzed primary tumor samples of 96 well-documented and longitudinally followed patients covering the whole spectrum of laryngeal neoplasia, including 21 patients with benign laryngeal diseases, 15 patients with dysplasia, 43 patients with early-stage carcinoma, and 17 patients with locally advanced carcinoma, for immunoreactivity of RelA, RelB, P50, and P52/P100, the main NF-κB subunits that activate transcription. Results were cross-examined with indices of tumor progression and survival. Interestingly, RelB expression increased with tumor stage, grade, and local extent. Moreover, patients displaying high RelB immunoreactivity exhibited statistically significantly poorer survival compared with patients featuring low levels of RelB expression (P = 0.018 by log-rank test). Using Cox regression analyses and tumor stage, local extent, grade and RelA/RelB immunoreactivity, we develop a new score that can independently predict survival of patients with laryngeal cancer. Hence we provide a simple and affordable NF-κB-based test to predict prognosis in laryngeal cancer.
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