Phosphorylation of gH2AX as a novel prognostic biomarker for laryngoesophageal dysfunction-free survival
| Autor: | María José de Miguel-Luken, Manuel Chaves-Conde, Begoña Quintana, Alicia Menoyo, Vladimir Suarez, David Chinchón, Verónica de Miguel-Luken, Amancio Carnero, Isabel Tirado, Jerónimo Pachón |
|---|---|
| Přispěvatelé: | Junta de Andalucía, Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), European Commission, Ministerio de Ciencia e Innovación (España), [Jose de Miguel-Luken, Maria] Virgen del Rocio Univ Hosp, Dept Med Oncol, Seville, Spain, [Chaves-Conde, Manuel] Virgen del Rocio Univ Hosp, Dept Med Oncol, Seville, Spain, [Quintana, Begona] Virgen del Rocio Univ Hosp, Dept Radiat Oncol, Seville, Spain, [Pachon, Jeronimo] Virgen del Rocio Univ Hosp, Dept Radiat Oncol, Seville, Spain, [Suarez, Vladimir] Virgen del Rocio Univ Hosp, Dept Radiat Oncol, Seville, Spain, [Menoyo, Alicia] Virgen del Rocio Univ Hosp, Dept Otorhinolaryngol, Seville, Spain, [Tirado, Isabel] Virgen del Rocio Univ Hosp, Dept Otorhinolaryngol, Seville, Spain, [de Miguel-Luken, Veronica] Univ Malaga, E-29071 Malaga, Spain, [Chinchon, David] Virgen del Rocio Univ Hosp, Dept Pathol, Seville, Spain, [Carnero, Amancio] Univ Seville, Inst Biomed Sevilla, IBIS Hosp Univ Virgen del Rocio, CSIC, Seville, Spain, Spanish Ministry of Economy and Competitivity, Plan Nacional de I+D+I, Plan Estatal de I+D+I, ISCIII - FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion, Consejeria de Salud of the Junta de Andalucia, ISCIII, FEDER |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Neck-cancer
0301 basic medicine Oncology Male Time Factors Laryngeal preservation larynx/laryngeal cancer medicine.medical_treatment Kaplan-Meier Estimate Histones 0302 clinical medicine Laryngeal cancer Risk Factors Medicine H2AX Phosphorylation Map17 gH2AX Chemoradiotherapy Middle Aged Treatment Outcome Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinoma Squamous Cell Disease Progression Biomarker (medicine) biomarker laryngeal cancer Female medicine.drug medicine.medical_specialty Squamous-cell carcinoma preservation Mtor Organ preservation Antineoplastic Agents Senescence DDR Disease-Free Survival 03 medical and health sciences Predictive Value of Tests Internal medicine Pathology Section Carcinoma Biomarkers Tumor Humans Laryngeal Neoplasms Proportional Hazards Models Retrospective Studies Cisplatin P53 Dose-Response Relationship Drug business.industry Proportional hazards model Squamous Cell Carcinoma of Head and Neck Replication stress Cancer Membrane Proteins Retrospective cohort study medicine.disease laryngeal preservation Research Paper: Pathology Surgery Radiation therapy 030104 developmental biology Ki-67 Antigen Neoplasm Recurrence Local Tumor Suppressor Protein p53 business Advanced laryngeal-cancer Head Biomarkers Dna-damage response |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Oncotarget |
| Popis: | 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. The authors thank the donors and the Andalusian Public Health System Biobank (ISCIII-Red de Biobancos RD12/0036/0017) for the human specimens used in this study. This work was supported by grants to from the Spanish Ministry of Economy and Competitivity, Plan Nacional de I+D+I 2008-2011, Plan Estatal de I+D+I 2013-2016, ISCIII (Fis: PI12/00137, PI15/00045, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). This work has been also possible thanks to the Plan Estatal de I+D+i 2013-2016, Grant PIE13/0004 co-funded by the ISCIII and FEDER funds. |
| Databáze: | OpenAIRE |
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