Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation

3q 致癌基因 SEC62 的表达可预测接受原发性化放疗治疗的头颈部鳞状细胞癌患者的生存率

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作者:Maximilian Linxweiler, Matthias Schneider, Sandrina Körner, Moritz Knebel, Lukas Alexander Brust, Felix Leon Braun, Silke Wemmert, Mathias Wagner, Markus Hecht, Bernhard Schick, Jan Philipp Kühn

Abstract

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients' overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated.

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