Background: Recurrent oral squamous cell carcinoma (re-OSCC) poses a serious therapeutic challenge and is linked to poor survival outcomes. SOX2 and NANOG, key transcription factors in cancer stem cell biology, may drive tumor progression and therapy resistance. However, their prognostic value in re-OSCC and their relationship to adjuvant therapy remain unclear. Methods: We retrospectively analyzed a single-center cohort of 94 patients with re-OSCC treated with curative intent via (1) surgery alone, (2) surgery plus adjuvant radiotherapy (RT), or (3) surgery plus adjuvant radiochemotherapy (RCT). Tissue microarrays (TMAs) were constructed from matched primary and recurrent tumors and immunohistochemical (IHC) staining for SOX2, and NANOG was quantified using H-scores. Post-recurrence overall survival (prOS) and post-recurrence disease-free survival (prDFS) were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: SOX2 expression and survival: Elevated SOX2 expression (H-score > 14) in re-OSCC was significantly associated with improved prOS (p= 0.013) and prDFS (p= 0.026). Notably, patients who had received adjuvant therapy (particularly RCT) showed higher SOX2 levels in recurrent tumors compared to those treated with surgery alone. NANOG expression and therapy: NANOG expression declined markedly from primary to recurrent tumors (median H-score 42.2 vs. 8.7;p< 0.001). This decline was most pronounced in patients treated with surgery alone. Despite this dynamic change, NANOG expression did not correlate significantly with prOS or prDFS. Other prognostic factors include advanced tumor stage (rT2–rT4) and lymph node involvement (rN+/x)m which remained significant predictors of worse survival in the recurrent setting, regardless of adjuvant therapy. Conclusion: SOX2 overexpression in re-OSCC correlates with better survival, suggesting a unique prognostic role distinct from primary disease. Adjuvant therapy, especially RCT, appears to maintain or elevate SOX2 levels, potentially contributing to improved treatment response. In contrast, although NANOG expression decreases in recurrence, particularly in patients who undergo surgery alone, it does not significantly affect survival outcomes. These findings underscore the importance of context-specific biomarker assessments and provide a rationale for incorporating SOX2 status into personalized treatment strategies for re-OSCC.
背景：复发性口腔鳞状细胞癌（re-OSCC）是临床治疗中的严峻挑战，且与不良生存结局相关。SOX2和NANOG作为肿瘤干细胞生物学中的关键转录因子，可能驱动肿瘤进展和治疗抵抗。然而，它们在re-OSCC中的预后价值及其与辅助治疗的关系尚不明确。方法：我们回顾性分析了94例以治愈为目的接受治疗的re-OSCC患者的单中心队列，治疗方式包括：（1）单纯手术，（2）手术联合辅助放疗（RT），或（3）手术联合辅助放化疗（RCT）。利用配对的初发和复发肿瘤组织构建组织芯片（TMAs），通过免疫组化（IHC）染色检测SOX2和NANOG表达，并使用H-score进行量化。采用Kaplan-Meier分析和Cox比例风险模型评估复发后总生存期（prOS）和复发后无病生存期（prDFS）。结果：SOX2表达与生存：re-OSCC中SOX2高表达（H-score > 14）与改善的prOS（p=0.013）和prDFS（p=0.026）显著相关。值得注意的是，与仅接受手术治疗的患者相比，接受过辅助治疗（尤其是RCT）的患者复发肿瘤中SOX2水平更高。NANOG表达与治疗：NANOG表达从初发到复发肿瘤显著下降（中位H-score 42.2 vs. 8.7；p<0.001）。这种下降在仅接受手术治疗的患者中最为明显。尽管存在这种动态变化，NANOG表达与prOS或prDFS无显著相关性。其他预后因素包括晚期肿瘤分期（rT2–rT4）和淋巴结受累（rN+/x），无论是否接受辅助治疗，这些因素在复发情况下仍是生存不良的显著预测因子。结论：re-OSCC中SOX2过表达与更好的生存相关，提示其具有不同于初发疾病的独特预后作用。辅助治疗，尤其是RCT，似乎能维持或提升SOX2水平，可能有助于改善治疗反应。相比之下，尽管NANOG在复发时表达下降（尤其在仅接受手术治疗的患者中），但其对生存结局无显著影响。这些发现强调了特定背景下生物标志物评估的重要性，并为将SOX2状态纳入re-OSCC个体化治疗策略提供了依据。
Prognostic Value of SOX2 and NANOG Expression in Recurrent Oral Squamous Cell Carcinoma
肿瘤(癌症)患者之家