The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer
EMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slu...
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doaj-387d5fb62e2c4645875e046e5ed7943b2021-02-13T00:03:40ZengMDPI AGCancers2072-66942021-02-011377277210.3390/cancers13040772The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck CancerHerbert Riechelmann0Teresa Bernadette Steinbichler1Susanne Sprung2Matthias Santer3Annette Runge4Ute Ganswindt5Gabriele Gamerith6Jozsef Dudas7Department for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Therapeutic Radiology and Oncology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Hematology and Oncology, Medical University Innsbruck, 6020 Innsbruck, AustriaDepartment for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaEMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slug expression was determined by IHC scoring in tumor specimens from patients with incident HNSCC. Patients were treated with either definitive radiotherapy or chemoradiotherapy (primary RT/CRT) or upfront surgery with or without postoperative RT or CRT (upfront surgery/PORT). Treatment failure rates and overall survival (OS) were compared between RT/CRT and upfront surgery/PORT in Slug-positive and Slug-negative patients. Slug IHC was positive in 91/354 HNSCC patients. Primary RT/CRT showed inferior response rates (univariate odds ratio (OR) for treatment failure, 3.6; 95% CI, 1.7 to 7.9; <i>p</i> = 0.001) and inferior 5-year OS (univariate, <i>p</i> < 0.001) in Slug-positive patients. The independent predictive value of Slug expression status was confirmed in a multivariable Cox model (<i>p</i> = 0.017). Slug-positive patients had a 3.3 times better chance of survival when treated with upfront surgery/PORT versus primary RT/CRT. For HNSCC patients, Slug IHC represents a novel and feasible predictive biomarker to support upfront surgery.https://www.mdpi.com/2072-6694/13/4/772head and neck cancerepithelial–mesenchymal transitionsnail family transcription factorsbiomarkerprognosisproportional hazards models |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Herbert Riechelmann Teresa Bernadette Steinbichler Susanne Sprung Matthias Santer Annette Runge Ute Ganswindt Gabriele Gamerith Jozsef Dudas |
spellingShingle |
Herbert Riechelmann Teresa Bernadette Steinbichler Susanne Sprung Matthias Santer Annette Runge Ute Ganswindt Gabriele Gamerith Jozsef Dudas The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer Cancers head and neck cancer epithelial–mesenchymal transition snail family transcription factors biomarker prognosis proportional hazards models |
author_facet |
Herbert Riechelmann Teresa Bernadette Steinbichler Susanne Sprung Matthias Santer Annette Runge Ute Ganswindt Gabriele Gamerith Jozsef Dudas |
author_sort |
Herbert Riechelmann |
title |
The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer |
title_short |
The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer |
title_full |
The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer |
title_fullStr |
The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer |
title_full_unstemmed |
The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer |
title_sort |
epithelial-mesenchymal transcription factor slug predicts survival benefit of up-front surgery in head and neck cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-02-01 |
description |
EMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slug expression was determined by IHC scoring in tumor specimens from patients with incident HNSCC. Patients were treated with either definitive radiotherapy or chemoradiotherapy (primary RT/CRT) or upfront surgery with or without postoperative RT or CRT (upfront surgery/PORT). Treatment failure rates and overall survival (OS) were compared between RT/CRT and upfront surgery/PORT in Slug-positive and Slug-negative patients. Slug IHC was positive in 91/354 HNSCC patients. Primary RT/CRT showed inferior response rates (univariate odds ratio (OR) for treatment failure, 3.6; 95% CI, 1.7 to 7.9; <i>p</i> = 0.001) and inferior 5-year OS (univariate, <i>p</i> < 0.001) in Slug-positive patients. The independent predictive value of Slug expression status was confirmed in a multivariable Cox model (<i>p</i> = 0.017). Slug-positive patients had a 3.3 times better chance of survival when treated with upfront surgery/PORT versus primary RT/CRT. For HNSCC patients, Slug IHC represents a novel and feasible predictive biomarker to support upfront surgery. |
topic |
head and neck cancer epithelial–mesenchymal transition snail family transcription factors biomarker prognosis proportional hazards models |
url |
https://www.mdpi.com/2072-6694/13/4/772 |
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