p62/SQSTM1 levels predicts radiotherapy resistance in hypopharyngeal carcinomas

p62/SQSTM1 水平可预测下咽癌的放射治疗耐药性

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作者:Akihito Arai, Tokuhiro Chano, Kaichiro Ikebuchi, Yusuke Hama, Yasuko Ochi, Hitosuke Tameno, Taketoshi Shimada

Abstract

Hypopharyngeal carcinoma is one of the worst prognostic malignancies among head and neck carcinomas. Therefore, a good biomarker should be identified to predict the best therapeutic option before starting the treatment. In cell models, p62/SQSTM1 levels affected the Nrf2-Keap1 pathway, ROS levels, GSH/GSSG ratios and cell growth, especially under irradiation rather than under CDDP exposure, which was toxic despite p62/SQSTM1 status. In a clinical cohort of hypopharyngeal carcinomas, high levels of p62/SQSTM1 significantly predicted poor prognosis (log-rank test, Chi-square value = 6.750, P = 0.0094) and maximum critical risk (Cox proportional hazard ratio = 4.405, P = 0.0086), especially in the radiotherapy group. Therefore, when p62/SQSTM1 is elevated in the biopsy section, hypopharyngeal carcinoma should be treated with surgical and/or chemotherapeutic options.

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