服用非那雄胺的前列腺增生患者前列腺轉(zhuǎn)錄組景觀特征分析
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Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride
ZHOU Lang1,LIU Ke1,LU Min2,BI Hai3,HUO Xiao4,MA Lulin1,LIU Cheng3
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.ConclusionFinasteride 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.
KEY WORDS:benign prostate hyperplasia;finasteride;transcriptome analysis;vascular endothelial growth factor D;CD38;androgen receptor
摘要:目的 通過轉(zhuǎn)錄組分析從基因表達(dá)方面探討非那雄胺對(duì)良性前列腺增生(BPH)患者的影響。(剩余11321字)