A link between RelB expression and tumor progression in laryngeal cancer.

Ioanna Giopanou,Ioannis Lilis,Theodoros Papadas,Helen Papadaki,Georgios T Stathopoulos

doi:10.18632/oncotarget.23109

Ioanna Giopanou, Ioannis Lilis + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.23109

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Abstract

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.

Highlights

Laryngeal cancer is the most frequent head and neck squamous cell carcinoma (HNSCC) with constantly decreasing five-year survival rates [1, 2]
We show how using this clinically relevant approach, RelB expression was found to increase with tumor stage, grade, and local extent and to portend poor survival, establishing it as a useful biomarker of prognosis in laryngeal cancer
Based on two previous reports that identified the cardinal significance of nuclear factor (NF)-κB signaling in HNSCC, we characterized the expression and subcellular localization of the main NF-κB pathway effector proteins in human laryngeal cancer

Summary

Introduction

Laryngeal cancer is the most frequent head and neck squamous cell carcinoma (HNSCC) with constantly decreasing five-year survival rates [1, 2]. A recent multi-platform analysis of the comprehensive genomes of 279 HNSCCs that included 72 laryngeal carcinomas identified aberrant activation of nuclear factor (NF)-κΒ as critical in the pathogenesis and for the development of new therapies [9]. NF-κB is mainly activated by nuclear translocation and activation of transcription by one or more of four subunits: RelA, RelB, P50, and P52/ P100. These ubiquitous proteins form cytoplasmic homoor heterodimers bound to inhibitors of NF-κB (ΙκΒ). A simple and cheap NF-κB-based test clinically useful to identify laryngeal cancer patients that face a poor prognosis is missing

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