Arai Akihito, Chano Tokuhiro, Ikebuchi Kaichiro, Hama Yusuke, Ochi Yasuko, Tameno Hitosuke, Shimada Taketoshi
Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of MedicineKajiicho 465, Kamigyo-ku, Kyoto, Kyoto 602-8566, Japan.
Department of Clinical Laboratory Medicine, Shiga University of Medical ScienceTsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan.
Am J Cancer Res. 2017 Apr 1;7(4):881-891. eCollection 2017.
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, = 0.0094) and maximum critical risk (Cox proportional hazard ratio = 4.405, = 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.
下咽癌是头颈癌中预后最差的恶性肿瘤之一。因此，在开始治疗前应确定一种良好的生物标志物，以预测最佳治疗方案。在细胞模型中，p62/SQSTM1水平影响Nrf2-Keap1通路、ROS水平、GSH/GSSG比值和细胞生长，尤其是在照射条件下，而不是在顺铂暴露条件下，顺铂暴露无论p62/SQSTM1状态如何均具有毒性。在下咽癌临床队列中，p62/SQSTM1高水平显著预示预后不良（对数秩检验，卡方值=6.750，P=0.0094）和最大临界风险（Cox比例风险比=4.405，P=0.0086），尤其是在放疗组。因此，当活检切片中p62/SQSTM1升高时，下咽癌应采用手术和/或化疗方案进行治疗。
