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现实生活中基底细胞癌和鲍温病对光动力疗法反应的肿瘤、基质和糖酵解标志物分析

Analysis of tumoral, stromal and glycolitic markers in the response basal cell carcinoma and Bowen disease to photodynamic therapy in real life.

作者信息

Bernal-Masferrer L, Gracia-Cazaña T, Najera-Botello L, Gomez-Mateo M C, Cerro P, Matei M C, Gallego-Rentero M, González S, Juarranz A, Gilaberte Y

机构信息

Department of Dermatology, Miguel Servet University Hospital, University of Zaragoza, IIS Aragón. Zaragoza, Spain.

Department of Dermatology, Miguel Servet University Hospital, University of Zaragoza, IIS Aragón. Zaragoza, Spain.

出版信息

Photodiagnosis Photodyn Ther. 2025 Feb;51:104442. doi: 10.1016/j.pdpdt.2024.104442. Epub 2024 Dec 10.

Abstract

BACKGROUND

Photodynamic therapy (PDT) is a widely-used non-surgical treatment for non-melanoma skin cancers, including basal cell carcinoma (BCC), actinic keratoses (AK), and Bowen's disease (BD). PDT has high success rates, but various factors, can influence treatment response. This study investigates the clinical, histological, and molecular factors that affect the efficacy of methyl aminolevulinate PDT (MAL-PDT) for BCC and BD.

METHODS AND PATIENTS

Prospective observational multicentric study performed between May 2019 and January 2021 with 64 patients included. Clinical data such as tumor thickness, location, and histological subtype were recorded. Immunohistochemical analysis was performed on tumor samples to assess the expression of biomarkers including p53, β-catenin, and GLUT1.

RESULTS

Tumor thickness was found to be a critical determinant of MAL-PDT response, with thicker nodular BCCs showing reduced response rates compared to thinner, superficial BCCs and BD lesions. Immunohistochemical analysis revealed that p53 positivity was associated with better treatment outcomes, while increased β-catenin and cytoplasmic GLUT1 expression correlated with resistance to PDT. On the other hand, the metabolic profile of the tumors indicated that tumors with higher glycolytic activity were less responsive to treatment, therefore, using metformin, a glycolytic inhibitor, as a potential adjuvant therapy to improve outcomes in resistant tumors should be considered.

CONCLUSION

This study emphasizes the importance of personalized approaches in the use of MAL-PDT, tailoring treatment according to tumor-specific characteristics. Biomarkers such as p53, β-catenin, and GLUT1 can serve as predictive tools for PDT response, helping clinicians identify patients who may benefit from alternative or combined treatments to enhance therapeutic efficacy.

摘要

背景

光动力疗法(PDT)是一种广泛应用于非黑色素瘤皮肤癌的非手术治疗方法,包括基底细胞癌(BCC)、光化性角化病(AK)和鲍恩病(BD)。PDT成功率高,但多种因素会影响治疗反应。本研究调查影响甲基氨基酮戊酸光动力疗法(MAL-PDT)治疗BCC和BD疗效的临床、组织学和分子因素。

方法与患者

2019年5月至2021年1月进行的前瞻性观察多中心研究,纳入64例患者。记录肿瘤厚度、位置和组织学亚型等临床数据。对肿瘤样本进行免疫组织化学分析,以评估包括p53、β-连环蛋白和葡萄糖转运蛋白1(GLUT1)在内的生物标志物的表达。

结果

发现肿瘤厚度是MAL-PDT反应的关键决定因素,与较薄的浅表性BCC和BD病变相比,较厚的结节性BCC反应率降低。免疫组织化学分析显示,p53阳性与更好的治疗结果相关,而β-连环蛋白和细胞质GLUT1表达增加与对PDT的耐药性相关。另一方面,肿瘤的代谢谱表明,糖酵解活性较高的肿瘤对治疗反应较差,因此,应考虑使用糖酵解抑制剂二甲双胍作为潜在的辅助治疗,以改善耐药肿瘤的治疗效果。

结论

本研究强调了在使用MAL-PDT时采用个性化方法的重要性,根据肿瘤的特定特征调整治疗方案。p53、β-连环蛋白和GLUTI等生物标志物可作为PDT反应的预测工具,帮助临床医生识别可能从替代或联合治疗中获益以提高治疗效果的患者。

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