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

By Maximilian Linxweiler, Matthias Schneider, S. Körner, M. Knebel, L. Brust, F. Braun, S. Wemmert, M. Wagner, M. Hecht, Bernhard Schick and 1 more. Cancers, 2023

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Simple Summary Head and neck cancer patients are frequently treated with primary chemoradiation, but response to therapy is hard to predict. In this study, we identified the expression of the SEC62 gene as a significant and independent predictor of patient outcome in a cohort of 127 head and neck cancer patients undergoing primary chemoradiation. Further significant prognostic factors indicating a significantly shortened overall and progression-free survival included response to therapy (RECIST1.1), lymph node metastases, distant metastases, tobacco consumption, recurrence of disease, and advanced clinical stage of disease. Together, SEC62 represents a promising and valid prognostic biomarker in this treatment setting of head and neck cancer. Its role in tumor cell biology and potential therapeutic strategies targeting SEC62 should be further investigated. 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.

Subfields: Genetics, Oncology, Otorhinolaryngology

View Paper: https://doi.org/10.3390/cancers16010098