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Title: Phosphorylation of gH2AX as a novel prognostic biomarker for laryngoesophageal dysfunction-free survival.
Authors: de Miguel-Luken, María José
Chaves-Conde, Manuel
Quintana, Begoña
Menoyo, Alicia
Tirado, Isabel
de Miguel-Luken, Verónica
Pachón, Jerónimo
Chinchón, David
Suarez, Vladimir
Carnero, Amancio
Keywords: DDR;H2AX;Pathology Section;biomarker;laryngeal cancer;laryngeal preservation
metadata.dc.subject.mesh: Antineoplastic Agents
Biomarkers, Tumor
Carcinoma, Squamous Cell
Disease Progression
Disease-Free Survival
Dose-Response Relationship, Drug
Head and Neck Neoplasms
Kaplan-Meier Estimate
Ki-67 Antigen
Laryngeal Neoplasms
Membrane Proteins
Middle Aged
Neoplasm Recurrence, Local
Predictive Value of Tests
Proportional Hazards Models
Retrospective Studies
Risk Factors
Squamous Cell Carcinoma of Head and Neck
Time Factors
Treatment Outcome
Tumor Suppressor Protein p53
Issue Date: 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.
metadata.dc.identifier.doi: 10.18632/oncotarget.9172
Appears in Collections:Producción 2020

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