Autor: |
Ziogas M; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, 50937 Cologne, Germany.; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University Hospital of Cologne, 50937 Cologne, Germany., Siefer O; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, 50937 Cologne, Germany.; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University Hospital of Cologne, 50937 Cologne, Germany., Wuerdemann N; Department of Internal Medicine, Faculty of Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, 50937 Cologne, Germany., Balaji H; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, 50937 Cologne, Germany.; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University Hospital of Cologne, 50937 Cologne, Germany., Gross E; Department of Neurology, University Hospital of Cologne, 50924 Cologne, Germany., Drebber U; Institute for Pathology, University Hospital of Cologne, 50937 Cologne, Germany., Klussmann JP; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, 50937 Cologne, Germany.; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University Hospital of Cologne, 50937 Cologne, Germany., Huebbers CU; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, 50937 Cologne, Germany.; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University Hospital of Cologne, 50937 Cologne, Germany. |
Abstrakt: |
Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53 WT ). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification ( p = 0.009) as well as positive HPV status ( p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. |