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光动力疗法治疗光化性角化病中增殖和炎症生物标志物(Ki67、p53和COX-2)的靶向研究

Targeting Biomarkers of Proliferation and Inflammation (Ki67, p53, and COX-2) in Actinic Keratoses with Photodynamic Therapy.

作者信息

Ceryn Justyna, Lesiak Aleksandra, Ciążyńska Magdalena, Sobolewska-Sztychny Dorota, Noweta Marcin, Stasikowska-Kanicka Olga, Ciążyński Karol, Zalaudek Iris, Narbutt Joanna

机构信息

Department of Dermatology, Paediatric Dermatology and Dermatological Oncology, Medical University of Lodz, 90-217 Lodz, Poland.

International Doctoral School, Medical University of Lodz, 90-647 Lodz, Poland.

出版信息

Biomedicines. 2025 Jun 17;13(6):1487. doi: 10.3390/biomedicines13061487.

DOI:10.3390/biomedicines13061487
PMID:40564206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12190994/
Abstract

: Actinic keratoses (AKs) are common pre-neoplastic lesions that may progress to cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) is an effective field-directed treatment for AK, but its impact on key biomarkers remains unclear. This study evaluates the clinical, dermatoscopic, and immunohistochemical effects of PDT on AK, with a focus on proliferation (Ki67, p53) and inflammation (COX-2) markers, to assess its efficacy in delaying carcinogenesis. : In our prospective one-center study, we enrolled 31 patients with AK, with no history of previous AK treatment. They underwent three PDT sessions at four-week intervals, with follow-up eight weeks after the final session. Clinical, dermatoscopic, and immunohistochemical analyses of Ki67, p53, and COX-2 expression were performed before and after treatment. : Clinically, 54.8% of patients achieved complete lesion clearance, with no residual severe AK lesions. Ki67 and p53 immunoexpression significantly decreased post-PDT ( < 0.05), confirming its antiproliferative effect. COX-2 expression also declined significantly ( < 0.05), supporting PDT's anti-inflammatory role. However, COX-2 remained stable or increased in 35.48% of cases, possibly due to inflammation-induced regeneration. There is a positive correlation between the reduction in Ki67, p53, and COX-2 immunoexpression and the decrease in AK severity (both according to Olsen grade and dermatoscopic grade). : PDT effectively reduces AK severity, proliferation, and inflammation markers, potentially delaying carcinogenesis. However, residual biomarker expression suggests that additional treatment sessions or combination therapies may be necessary for complete lesion clearance. Further studies are required to optimize PDT protocols.

摘要

光化性角化病(AKs)是常见的癌前病变,可能进展为皮肤鳞状细胞癌(cSCC)。光动力疗法(PDT)是一种有效的针对AK的局部治疗方法,但其对关键生物标志物的影响尚不清楚。本研究评估PDT对AK的临床、皮肤镜和免疫组化效果,重点关注增殖(Ki67、p53)和炎症(COX-2)标志物,以评估其在延缓癌变方面的疗效。

在我们的前瞻性单中心研究中,我们纳入了31例无既往AK治疗史的AK患者。他们每隔四周接受三次PDT治疗,并在最后一次治疗后八周进行随访。在治疗前后对Ki67、p53和COX-2表达进行临床、皮肤镜和免疫组化分析。

临床上,54.8%的患者病变完全清除,无残留严重AK病变。PDT后Ki67和p53免疫表达显著降低(<0.05),证实了其抗增殖作用。COX-2表达也显著下降(<0.05),支持PDT的抗炎作用。然而,35.48%的病例中COX-2保持稳定或升高,可能是由于炎症诱导的再生。Ki67、p53和COX-2免疫表达的降低与AK严重程度的降低之间存在正相关(根据奥尔森分级和皮肤镜分级)。

PDT有效地降低了AK的严重程度、增殖和炎症标志物,可能延缓癌变。然而,残留的生物标志物表达表明,可能需要额外的治疗疗程或联合治疗才能完全清除病变。需要进一步研究以优化PDT方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/81d1df997f07/biomedicines-13-01487-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/46680c759392/biomedicines-13-01487-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/ddf482378cc1/biomedicines-13-01487-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/81d1df997f07/biomedicines-13-01487-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/46680c759392/biomedicines-13-01487-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/ddf482378cc1/biomedicines-13-01487-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af4/12190994/81d1df997f07/biomedicines-13-01487-g003.jpg

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本文引用的文献

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Cancers (Basel). 2025 Feb 19;17(4):703. doi: 10.3390/cancers17040703.
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Molecular Biomarkers in Cutaneous Photodynamic Therapy: A Comprehensive Review.皮肤光动力疗法中的分子生物标志物:综述
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European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).
欧洲基于共识的跨学科指南:光化性角化病、上皮紫外线诱导发育不良和皮肤癌前病变的诊断、治疗和预防,代表了欧洲皮肤病肿瘤学会、欧洲皮肤病学会、欧洲皮肤性病学会和医学专家联盟(Union Européenne des Médecins Spécialistes)。
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Expression of p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 Markers in Actinic Keratosis, In Situ Squamous Cell Carcinoma and Normal Sun-Exposed Skin of Elderly Patients.p53、p63、p16、Ki67、细胞周期蛋白D、Bcl-2和CD31标志物在老年患者日光性角化病、原位鳞状细胞癌及正常暴露日光皮肤中的表达
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Clinical Characteristics of Actinic Keratosis Associated with the Risk of Progression to Invasive Squamous Cell Carcinoma: A Systematic Review.与进展为浸润性鳞状细胞癌风险相关的光化性角化病的临床特征:一项系统评价
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Topical Treatment of Actinic Keratosis and Metalloproteinase Expression: A Clinico-Pathological Retrospective Study.光化性角化病的局部治疗与金属蛋白酶表达:一项临床病理回顾性研究。
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