title: Phosphorylation of gH2AX as a novel prognostic biomarker for laryngoesophageal dysfunction-free survival.
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.
authors.affiliation: Department of Medical Oncology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: de Miguel-Luken
authors.affiliation: Department of Medical Oncology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Chaves-Conde
authors.affiliation: Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Quintana
authors.affiliation: Department of Otorhinolaryngology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Menoyo
authors.affiliation: Department of Otorhinolaryngology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Tirado
authors.affiliation: University of Málaga, Málaga, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: de Miguel-Luken
authors.affiliation: Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: Department of Pathology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Chinchón
authors.affiliation: Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Suarez
authors.affiliation: Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/ Consejo Superior de Investigaciones Científicas, Seville, Spain.
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006657:Histones / Q000032:analysis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones; D019394:Ki-67 Antigen; D008565:Membrane Proteins; C509768:PDZK1IP1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
keywords: DDR; H2AX; Pathology Section; biomarker; laryngeal cancer; laryngeal preservation