Linxweiler Maximilian, Schneider Matthias, Körner Sandrina, Knebel Moritz, Brust Lukas Alexander, Braun Felix Leon, Wemmert Silke, Wagner Mathias, Hecht Markus, Schick Bernhard, Kühn Jan Philipp
Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, D-66421 Homburg, Germany.
Department of General and Surgical Pathology, Saarland University Medical Center, D-66421 Homburg, Germany.
Cancers (Basel). 2023 Dec 24;16(1):98. doi: 10.3390/cancers16010098.
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 ( = 0.015) and advanced lymph node metastases ( = 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 ( = 0.046) and response to therapy ( < 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.
原发性放化疗(CRT)是局部晚期头颈部鳞状细胞癌(HNSCC)既定的治疗选择,通常是将调强放疗与铂类同步化疗相结合。尽管大多数患者可以通过这种方案治愈,但治疗反应高度异质性,且很难预测。SEC62是一种转移促进癌基因,在各种癌症实体中经常过度表达,并与不良预后相关。其在接受CRT的HNSCC患者中的作用迄今尚未得到研究。本研究纳入了127例接受原发性CRT治疗的HNSCC患者。中位随访时间为5.4年。原发性肿瘤的治疗前组织样本用于针对SEC62的免疫组织化学检测。在单变量和多变量生存分析中,对SEC62表达、临床和组织病理学参数以及患者预后进行了相关性分析。SEC62高表达与显著缩短的总生存期(P = 0.015)和晚期淋巴结转移(P = 0.024)相关。总生存期和无进展生存期较差的其他显著预测因素包括治疗反应(RECIST1.1)、淋巴结状态、远处转移、吸烟、疾病复发和国际抗癌联盟(UICC)分期。在多变量Cox比例风险回归分析中,只有SEC62表达(P = 0.046)和治疗反应(P < 0.0001)作为患者总生存期的独立预测因素保持统计学意义。本研究确定SEC62是接受原发性CRT治疗的HNSCC患者的独立预后生物标志物。SEC62作为潜在治疗靶点的作用及其与头颈癌细胞辐射诱导分子改变的相互作用应进一步研究。