现代泌尿外科杂志2024,Vol.29Issue(2) :101-107,153.DOI:10.3969/j.issn.1009-8291.2024.02.002

服用非那雄胺的前列腺增生患者前列腺转录组景观特征分析

Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride

周朗 刘可 陆敏 毕海 霍霄 马潞林 刘承
现代泌尿外科杂志2024,Vol.29Issue(2) :101-107,153.DOI:10.3969/j.issn.1009-8291.2024.02.002

服用非那雄胺的前列腺增生患者前列腺转录组景观特征分析

Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride

周朗 1刘可 1陆敏 2毕海 3霍霄 4马潞林 1刘承3
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作者信息

  • 1. 北京大学第三医院 泌尿外科 北京 100191
  • 2. 北京大学第三医院 病理科,北京 100191
  • 3. 上海交通大学医学院附属第一人民医院泌尿外科临床医学中心,上海 200080
  • 4. 北京大学第三医院医学创新研究院基础医学研究中心,北京 100191
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摘要

目的 通过转录组分析从基因表达方面探讨非那雄胺对良性前列腺增生(BPH)患者的影响.方法 收集2020年10月—2021年10月于北京大学第三医院接受前列腺电切术的患者,根据患者术前是否长期(>6个月)服用非那雄胺分为用药组和非用药组,两组各8例.对两组患者的前列腺组织标本进行转录组测序分析,定量聚合酶链式反应(qPCR)及免疫组化分析验证其结果.结果 用药组与非用药组相比,上调基因857个,下调基因806个.通路富集分析显示,非那雄胺导致焦点粘附通路中血管内皮生长因子D型(VEGFD)表达下调;组间网络分析提示钙信号通路为整个过程的关键通路;进一步对其进行基因集富集分析(GSEA)发现分化簇38(CD38)基因表达上调.qPCR及免疫组化验证支持上述转录组结果,同时发现雄激素受体表达升高.结论 非那雄胺通过下调焦点粘附通路中VEGFD的表达减少前列腺微血管生成,进而降低BPH手术出血的风险,长期服用非那雄胺导致钙信号通路中CD38表达上调,可能与非那雄胺抵抗有关.

Abstract

Objective To explore the effects of finasteride on the gene expression in patients with benign prostatic hyperplasia(BPH)through transcriptome analysis.Methods Postoperative prostate tissues from patients who underwent prostatectomy at Peking University Third Hospital during Oct.2020 and Oct.2021 were collected.The patients were divided into medication group and non-medication group based on whether they had taken finasteride for a long time before surgery,with 8 patients in either groups.Transcriptome sequencing analysis was performed and the results were validated with qPCR and immunohistochemistry analysis.Results Compared with the non-medication group,857 up-regulated and 806 down-regulated genes were screened in the medication group.Pathway enrichment analysis showed that finasteride induced down-regulation of vascular endothelial growth factor D(VEGFD)expression in the focal adhesion pathway.Inter group network analysis suggested that the calcium signaling pathway was key in the entire process.GSEA enrichment analysis further revealed the up regulation of CD38 gene expression in the calcium signaling pathway.The qPCR and immunohistochemistry analysis supported the transcriptome results mentioned above,and found that androgen receptor(AR)expression was also increased.Conclusion Finasteride reduces prostate microvascular formation by downregulating the expression of VEGFD in the focal adhesion pathway,thereby reducing the risk of bleeding during prostate hyperplasia surgery.Long-term use of finasteride leads to the up regulation of CD38 expression in the calcium signaling pathway,which may lead to the development of finasteride resistance.

关键词

良性前列腺增生/非那雄胺/转录组分析/血管内皮生长因子D型/分化簇38/雄激素受体

Key words

benign prostate hyperplasia/finasteride/transcriptome analysis/vascular endothelial growth factor D/CD38/androgen receptor

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基金项目

国家自然科学基金(82070778)

出版年

2024
现代泌尿外科杂志
西安交通大学

现代泌尿外科杂志

CSTPCD
影响因子:1.106
ISSN:1009-8291
参考文献量22
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