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男性生殖器硬化性苔藓、分化型阴茎上皮内瘤变及阴茎鳞状细胞癌中的Wnt信号传导

Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma.

作者信息

Kravvas Georgios, Xie Boyu, Millar Michael, Freeman Alex, Haider Aiman, Alnajjar Hussain M, Muneer Asif, Ahmed Aamir, Bunker Christopher Barry

机构信息

Department of Dermatology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

Cell and Developmental Biology, Division of Biosciences, University College London, London, United Kingdom.

出版信息

JID Innov. 2025 Apr 11;5(4):100372. doi: 10.1016/j.xjidi.2025.100372. eCollection 2025 Jul.

DOI:10.1016/j.xjidi.2025.100372
PMID:40486660
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12141826/
Abstract

INTRODUCTION

Male genital lichen sclerosus (MGLSc) is a chronic inflammatory disease causing scarring and significant morbidity, and predisposing individuals to differentiated penile intraepithelial neoplasia (dPeIN) and penile squamous cell carcinoma (PeSCC). Penile carcinogenesis follows two pathways: HPV-related and non-HPV-related. While HPV drives undifferentiated PeIN and warty/basaloid PeSCC, MGLSc is implicated in non-HPV-related dPeIN and "usual" PeSCC. Wnt signalling, pivotal in carcinogenesis, remains underexplored in MGLSc and PeIN.

METHODS

Tissue arrays from 114 archival samples of MGLSc, dPeIN, and PeSCC were analyzed using multi-label fluorescence staining and confocal microscopy for Wnt4, cyclin D1, c-MYC, and MMP7 expression.

RESULTS

Wnt signalling proteins were upregulated in PeSCC: cyclin D1 (2.3-fold), Wnt4 (2-fold), c-MYC (2.5-fold), and MMP7 (1.8-fold). Wnt4 expression increased in MGLSc (p=0.02), while dPeIN showed minimal changes. Altered co-localization of Wnt4/MMP7 (p=0.04) was observed in MGLSc and significant co-localization alterations of several protein pairs were also identified in PeSCC.

CONCLUSION

Wnt signalling plays a role in progression from MGLSc to PeSCC through protein dysregulation. Overexpression and altered interactions in PeSCC highlight its potential as a diagnostic, prognostic, and therapeutic target.

摘要

引言

男性生殖器硬化性苔藓（MGLSc）是一种慢性炎症性疾病，可导致瘢痕形成和严重的发病率，并使个体易患分化型阴茎上皮内瘤变（dPeIN）和阴茎鳞状细胞癌（PeSCC）。阴茎癌发生遵循两条途径：HPV相关途径和非HPV相关途径。虽然HPV驱动未分化的PeIN和疣状/基底样PeSCC，但MGLSc与非HPV相关的dPeIN和“普通”PeSCC有关。Wnt信号通路在癌症发生中起关键作用，在MGLSc和PeIN中仍未得到充分研究。

方法

使用多标记荧光染色和共聚焦显微镜分析114份MGLSc、dPeIN和PeSCC存档样本的组织芯片中Wnt4、细胞周期蛋白D1、c-MYC和MMP7的表达。

结果

Wnt信号蛋白在PeSCC中上调：细胞周期蛋白D1（2.3倍）、Wnt4（2倍）、c-MYC（2.5倍）和MMP7（1.8倍）。Wnt4表达在MGLSc中增加（p=0.02），而dPeIN变化最小。在MGLSc中观察到Wnt4/MMP7的共定位改变（p=0.04），在PeSCC中也发现了几对蛋白的显著共定位改变。

结论

Wnt信号通路通过蛋白质失调在从MGLSc进展到PeSCC中起作用。PeSCC中的过表达和相互作用改变突出了其作为诊断、预后和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/dc12910267a4/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/fac9a595f60c/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/3ef286ea2ebe/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/70d16d7296cf/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/d6b7b116aa2d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/c1c1a3ff7de4/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/557be1ceba56/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/a9f55e818406/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/e3a61c7a4b34/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/30d3389b6a51/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/dc12910267a4/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/fac9a595f60c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/bae1286caaf1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/c74cc7d62c8a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/3ef286ea2ebe/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/70d16d7296cf/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/d6b7b116aa2d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/c1c1a3ff7de4/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/557be1ceba56/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/a9f55e818406/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/e3a61c7a4b34/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/30d3389b6a51/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a97/12141826/dc12910267a4/gr12.jpg

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Expression of Wnt signaling proteins in rare congenital bladder disorders.Wnt信号蛋白在罕见先天性膀胱疾病中的表达
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Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.
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WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme.WNT/RYK 信号在肺间质中作为抗炎调节剂发挥作用。
Proc Natl Acad Sci U S A. 2022 Jun 14;119(24):e2201707119. doi: 10.1073/pnas.2201707119. Epub 2022 Jun 7.
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