二甲双胍对非糖尿病患者口腔鳞状细胞癌缺氧相关基因表达的影响——一项前瞻性机会窗研究
Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.
作者信息
Mueller Simon A, Elicin Olgun, Monney Bastien, Rau Tilman, Pra Alan Dal, Sachs Ludwig, Ramos Irene Centeno, Vassella Erik, Dammann Florian, Caparrotti Francesca, Limacher Andreas, Nisa Lluís, Dettmer Matthias S, Giger Roland
机构信息
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
出版信息
Eur Arch Otorhinolaryngol. 2025 Jun 4. doi: 10.1007/s00405-025-09493-8.
PURPOSE
Research suggests that metformin may reduce tumor hypoxia, rendering it a potential radiosensitizer. This study investigated metformin's effect on hypoxia-associated gene expression in oral cavity squamous cell carcinoma (OCSCC).
METHODS
In this prospective trial, non-diabetic patients with OCSCC scheduled for curative surgery received preoperative metformin for 10 to 14 days. Tumor biopsies were taken before and after metformin treatment. Gene expression profiling was performed using RNASeq, emphasizing on hypoxia-associated signaling pathways.
RESULTS
Fifteen patients of 25 enrolled patients completed the study protocol and passed quality checks. No significant difference in gene expression was observed after adjustment for multiple testing. No significant changes were found in the hypoxia-associated hypoxia-inducible factor 1- alpha (HIF1A) pathway or in other signaling pathways associated with metformin reported in the literature.
CONCLUSION
This study does not support the hypothesis that metformin improves tumor hypoxia in OCSCC after 10 to 14 days of treatment.
目的
研究表明二甲双胍可能会减轻肿瘤缺氧状况，使其成为一种潜在的放射增敏剂。本研究调查了二甲双胍对口腔鳞状细胞癌（OCSCC）中缺氧相关基因表达的影响。
方法
在这项前瞻性试验中，计划接受根治性手术的非糖尿病OCSCC患者术前服用二甲双胍10至14天。在二甲双胍治疗前后进行肿瘤活检。使用RNA测序进行基因表达谱分析，重点关注缺氧相关信号通路。
结果
25名入组患者中有15名完成了研究方案并通过了质量检查。在进行多重检验校正后，未观察到基因表达有显著差异。在缺氧相关的缺氧诱导因子1-α（HIF1A）通路或文献中报道的与二甲双胍相关的其他信号通路中未发现显著变化。
结论
本研究不支持二甲双胍在治疗10至14天后可改善OCSCC肿瘤缺氧状况这一假设。
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