Oncotarget

Research Papers: Pathology:

Phosphorylation of gH2AX as a novel prognostic biomarker for laryngoesophageal dysfunction-free survival

María José de Miguel-Luken, Manuel Chaves-Conde, Begoña Quintana, Alicia Menoyo, Isabel Tirado, Verónica de Miguel-Luken, Jerónimo Pachón, David Chinchón, Vladimir Suarez and Amancio Carnero _

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Oncotarget. 2016; 7:31723-31737. https://doi.org/10.18632/oncotarget.9172

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Abstract

María José de Miguel-Luken1, Manuel Chaves-Conde1, Begoña Quintana2, Alicia Menoyo3, Isabel Tirado3, Verónica de Miguel-Luken4, Jerónimo Pachón2, David Chinchón5, Vladimir Suarez2 and Amancio Carnero6

1 Department of Medical Oncology, Virgen del Rocío University Hospital, Seville, Spain

2 Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville, Spain

3 Department of Otorhinolaryngology, Virgen del Rocío University Hospital, Seville, Spain

4 University of Málaga, Málaga, Spain

5 Department of Pathology, Virgen del Rocío University Hospital, Seville, Spain

6 Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/ Consejo Superior de Investigaciones Científicas, Seville, Spain

Correspondence to:

Amancio Carnero, email:

Keywords: laryngeal cancer, H2AX, biomarker, laryngeal preservation, DDR, Pathology Section

Received: November 03, 2015 Accepted: April 22, 2016 Published: May 04, 2016

Abstract

Current larynx preservation treatments have achieved an improvement of laryngoesophageal dysfunction-free survival (LDS) but lead to significant toxicities and recurrences. At present, there is no evidence to select the group of patients that may benefit from preservation approaches instead of surgery. Therefore, laryngeal biomarkers could facilitate pretreatment identification of patients who could respond to chemoradiation-based therapy. In this study, we evaluated retrospectively 53 patients with larynx cancer to determine whether gH2AX phosphorylation (pH2AX) alone or in combination with the membrane protein MAP17 (PDZK1IP1) could be used as prognostic biomarkers. We also evaluated whether the completion of cisplatin treatment and radiotherapy could predict survival in combination with pH2AX.

We found that the dose of cisplatin received but not the length of the radiotherapy influenced LDS. High-pH2AX expression was associated with prolonged LDS (HR 0.26, p = 0.02) while MAP17 correlated with overall survival (OS) (HR 0.98, p = 0.05). High-MAP17 and high-pH2AX combined analysis showed improved LDS (with 61.35 months vs 32.2 months, p = 0.05) and OS (with 66.6 months vs 39.8 months, p = 0.01). Furthermore, the subgroup of high-pH2AX and optimal dose of cisplatin was also associated with OS (72 months vs 38.6 months, p = 0.03) and LDS (66.9 months vs 27 months, p = 0.017). These findings suggest that pH2AX alone or better in combination with MAP17 may become a novel and valuable prognostic biomarker for patients with laryngeal carcinoma treated with preservation approaches.


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