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EpCAM生物标志物在膀胱癌中的临床价值及其与免疫细胞浸润的关联。

The clinical value of the EpCAM biomarker and its association with immune cell infiltration in bladder cancer.

作者信息

Nedjadi Taoufik, Ahmed Mohamed E, Ansari Hifzur R, Aouabdi Sihem, Samkari Alaa, Al-Maghrabi Jaudah

机构信息

King Abdullah International Medical Research Centre, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, 21423, Saudi Arabia.

Faculty of Basic Sciences, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, 21423, Saudi Arabia.

出版信息

Diagn Pathol. 2025 Aug 25;20(1):96. doi: 10.1186/s13000-025-01696-1.

DOI:10.1186/s13000-025-01696-1
PMID:40855306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12376368/
Abstract

BACKGROUND

Bladder cancer is characterized by its heterogeneous nature and high propensity for recurrence and progression. The absence of reliable diagnostic and prognostic biomarkers to accurately identify high-risk patients further complicates the clinical management of the disease. MOC-31, an antibody that targets epithelial cell adhesion molecule (EpCAM), is utilized to distinguish between mesothelioma and metastatic cancer, but its clinical utility, prognostic value and functional dynamics in bladder cancer have yet to be verified.

METHODS

A comprehensive analysis of EpCAM expression and its associations with key clinicopathological parameters was performed via The Cancer Genome Atlas (TCGA). Additionally, we retrospectively assessed EpCAM expression in our bladder cancer cohort using MOC-31 antibody and examined its prognostic value and correlation with clinicopathological features. The cBioPortal, STRING and TIMER databases were used to explore the interactions between EpCAM expression, immune cell infiltration and immune checkpoint genes.

RESULTS

The difference in EpCAM expression varied widely across various cancer types and was strongly correlated with advanced cancer stage. EpCAM staining with MOC-31 exhibited membranous positivity in 51.7% of the analysed cohort. Kaplan-Meier survival analysis revealed a discernible trend suggesting a poorer prognosis for patients with low EpCAM expression than for those with high EpCAM expression. Protein-protein interaction demonstrated that EFGR, HER2 and Claudin-7 are key EpCAM interactors. A strong association was observed between EpCAM expression and immune cell infiltration as well as immune-related genes.

CONCLUSION

This study highlights the prognostic value of EpCAM in bladder cancer, revealing a strong link between EpCAM expression and disease pathogenesis. These results underscore the need for further research to validate these findings and explore the significance of EpCAM as a therapeutic target in managing bladder cancer.

摘要

背景

膀胱癌具有异质性,且复发和进展倾向高。缺乏可靠的诊断和预后生物标志物来准确识别高危患者,进一步使该疾病的临床管理复杂化。MOC-31是一种靶向上皮细胞粘附分子(EpCAM)的抗体,用于区分间皮瘤和转移性癌,但其在膀胱癌中的临床效用、预后价值和功能动态尚未得到验证。

方法

通过癌症基因组图谱(TCGA)对EpCAM表达及其与关键临床病理参数的关联进行了综合分析。此外,我们使用MOC-31抗体回顾性评估了我们膀胱癌队列中的EpCAM表达,并检查了其预后价值以及与临床病理特征的相关性。利用cBioPortal、STRING和TIMER数据库探索EpCAM表达、免疫细胞浸润和免疫检查点基因之间的相互作用。

结果

EpCAM表达在不同癌症类型中的差异广泛,且与癌症晚期密切相关。用MOC-31进行的EpCAM染色在51.7%的分析队列中表现为膜阳性。Kaplan-Meier生存分析显示出一种明显的趋势,表明EpCAM低表达患者的预后比高表达患者更差。蛋白质-蛋白质相互作用表明,EFGR、HER2和Claudin-7是EpCAM的关键相互作用分子。观察到EpCAM表达与免疫细胞浸润以及免疫相关基因之间存在密切关联。

结论

本研究突出了EpCAM在膀胱癌中的预后价值,揭示了EpCAM表达与疾病发病机制之间的紧密联系。这些结果强调需要进一步研究以验证这些发现,并探索EpCAM作为膀胱癌治疗靶点的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/0fe01e692a7d/13000_2025_1696_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/d92adc58da02/13000_2025_1696_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/20eb46e942df/13000_2025_1696_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/0fe01e692a7d/13000_2025_1696_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/d92adc58da02/13000_2025_1696_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/20eb46e942df/13000_2025_1696_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6384/12376368/0fe01e692a7d/13000_2025_1696_Fig4_HTML.jpg

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本文引用的文献

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Regulation of the Function and Expression of EpCAM.上皮细胞黏附分子(EpCAM)功能与表达的调控
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Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma.
综合分析揭示了上皮细胞黏附分子(EpCAM)在肾透明细胞癌中的双重生物学功能作用。
Heliyon. 2023 Dec 14;10(1):e23505. doi: 10.1016/j.heliyon.2023.e23505. eCollection 2024 Jan 15.
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Smoking, ethnicity and bladder cancer - implications for public health and clinical practice.吸烟、种族与膀胱癌——对公共卫生和临床实践的影响
Nat Rev Urol. 2023 Nov;20(11):643-644. doi: 10.1038/s41585-023-00804-4.
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The Regulatory Mechanism of EpCAM N-Glycosylation-Mediated MAPK and PI3K/Akt Pathways on Epithelial-Mesenchymal Transition in Breast Cancer Cells.上皮细胞黏附分子 N-糖基化调控乳腺癌细胞上皮间质转化过程中 MAPK 和 PI3K/Akt 信号通路的机制研究
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