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 (p53WT). 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.
头颈部鳞状细胞癌(HNSCC),尤其是口咽鳞状细胞癌(OPSCC),因其发病率不断上升和高死亡率而成为全球重大健康挑战。本研究探讨了醛酮还原酶1C2(AKR1C2)在OPSCC中的作用,重点关注其表达情况、与人乳头瘤病毒(HPV)状态、氧化应激状态及临床结局的相关性,并特别强调性别特异性差异。我们采用免疫组织化学方法分析了51例OPSCC患者福尔马林固定、石蜡包埋组织样本中AKR1C2的表达。此外,我们在培养的HPV16-E6*I和HPV16-E6过表达的HEK293细胞系(p53WT)中进行了RT-qPCR分析。通过统计分析评估AKR1C2表达与患者数据之间的相关性。结果显示,AKR1C2表达升高与更高的AJCC分期(p=0.009)以及HPV阳性状态(p=0.008)显著相关。AKR1C2的预后意义因性别而异:AKR1C2高表达的女性患者总生存期更长,而男性患者预后较差。此外,AKR1C2表达与HPV状态相关,提示可能存在HPV特异性调控机制。这些发现强调了AKR1C2、HPV和患者性别之间复杂的相互作用,凸显了对OPSCC进行个体化治疗策略的必要性。考虑到性别差异,靶向抑制AKR1C2可能改善治疗效果。未来研究应深入探讨这些机制,以提高治疗疗效。