Falougy Mohamed, Taubitz Clara, Ragab Mohab, Patil Akshay, Jensen Justus, Hoppe Steffen, Kümpers Christiane, Ribbat-Idel Julika, Rades Dirk, Hakim Samer George
Department of Oral and Maxillofacial Surgery, Head and Neck Cancer Center, University Hospital Schleswig-Holstein, 23562 Lübeck, Germany.
Department of Internal Medicine II, Klinikum Rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany.
Cancers (Basel). 2025 Mar 31;17(7):1181. doi: 10.3390/cancers17071181.
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.
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.
SOX2 expression and survival: Elevated SOX2 expression (H-score > 14) in re-OSCC was significantly associated with improved prOS ( = 0.013) and prDFS ( = 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; < 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.
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.
复发性口腔鳞状细胞癌（re-OSCC）带来了严峻的治疗挑战，且与不良生存结局相关。SOX2和NANOG是癌症干细胞生物学中的关键转录因子，可能推动肿瘤进展和治疗抵抗。然而，它们在re-OSCC中的预后价值以及与辅助治疗的关系仍不明确。
我们回顾性分析了一个单中心队列中94例接受根治性治疗的re-OSCC患者，这些患者接受了以下治疗：（1）单纯手术，（2）手术加辅助放疗（RT），或（3）手术加辅助放化疗（RCT）。组织微阵列（TMA）由匹配的原发性和复发性肿瘤构建而成，并进行SOX2的免疫组织化学（IHC）染色，使用H评分对NANOG进行定量。采用Kaplan-Meier分析和Cox比例风险模型评估复发后总生存（prOS）和复发后无病生存（prDFS）。
SOX2表达与生存：re-OSCC中SOX2表达升高（H评分>14）与prOS改善（P = 0.013）和prDFS改善（P = 0.026）显著相关。值得注意的是，与单纯接受手术治疗的患者相比，接受辅助治疗（尤其是RCT）的患者复发性肿瘤中SOX2水平更高。NANOG表达与治疗：从原发性肿瘤到复发性肿瘤，NANOG表达显著下降（中位H评分42.2对8.7；P<0.001）。这种下降在单纯接受手术治疗的患者中最为明显。尽管有这种动态变化，但NANOG表达与prOS或prDFS无显著相关性。其他预后因素包括肿瘤晚期（rT2 - rT4）和淋巴结受累（rN+/x），无论辅助治疗如何，这些因素仍然是复发情况下生存较差的显著预测因素。
re-OSCC中SOX2过表达与更好的生存相关，表明其具有与原发性疾病不同的独特预后作用。辅助治疗，尤其是RCT，似乎能维持或提高SOX2水平，可能有助于改善治疗反应。相比之下，尽管NANOG表达在复发时下降，尤其是在单纯接受手术的患者中，但它并未显著影响生存结局。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的个性化治疗策略提供了理论依据。
