Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9Highshowed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-β pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.
头颈部鳞状细胞癌（HNSCC）的患者预后存在显著差异。据报道，SOX2在多种癌症类型的增殖、肿瘤生长、耐药性和转移中发挥作用。此外，SOX9与免疫耐受和治疗失败有关。SOX2和SOX9通过一种尚未阐明的分子机制诱导治疗失败。本研究探讨了SOX2/SOX9的负相关关系及其在肿瘤中的差异性表达，如何影响肿瘤微环境和放疗反应。通过公共RNA测序数据、人体活检样本和基因敲低细胞模型，我们探究了SOX2与SOX9表达倒置的影响。研究发现，与SOX2高表达/SOX9低表达的患者相比，SOX2低表达/SOX9高表达的患者生存率降低。根据放疗和人乳头瘤病毒感染状态对患者进行分层后的生存分析进一步揭示了其临床相关性。我们鉴定出一组由SOX2/SOX9表达倒置新发现的候选基因构成的基因集特征。此外，TGF-β通路被预测为这些候选基因过表达的重要贡献者。体外实验结果表明，沉默SOX2可增强肿瘤的放射抗性，而沉默SOX9则增强放射敏感性。这些发现为进一步研究转录因子在优化HNSCC治疗中的潜在应用价值奠定了基础。
The Role of SOX2 and SOX9 in Radioresistance and Tumor Recurrence
肿瘤(癌症)患者之家