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对良性前列腺增生症的转录组分析确定了前列腺过度生长和对5-α减少酶抑制剂耐药性的关键途径

Renjie Jin¹, Connor M Forbes^1,2, Nicole L Miller¹

¹Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

|January 3, 2024

概括

这项研究表明,参与前列腺发育的途径在良性前列腺增生 (BPH) 中被重新激活. 了解这些途径为BPH和下泌尿道症状 (LUTS) 提供了新的治疗点.

科学领域:

泌尿器科泌尿器科泌尿器科泌尿器科
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

良性前列腺增生 (BPH) 影响了许多男性,医学疗法显示出可变的反应率.
之前的研究表明,随着5α-减少酶抑制剂 (5ARI) 治疗,前列腺葡萄糖皮质水平增加,可能会影响前列腺生长.
这项研究旨在阐明BPH的转录组变化及其与5ARI治疗和葡萄糖皮质体效应的关系.

研究的目的:

为了确定BPH组织和正常的前列腺组织之间的转录组差异.
研究5α-减少酶抑制剂 (5ARI) 治疗对BPH基因表达的影响.
探索葡萄糖皮质激素在前列腺上皮质分支形态发生的作用及其与BPH的相关性.

主要方法:

在手术性BPH (S-BPH) 和偶发性BPH (I-BPH) 组织上进行了大量RNA测序.
接受5ARI治疗的患者的基因表达数据与未接受治疗的患者进行了比较.
一个3D人类前列腺细胞培养模型被用于研究葡萄糖皮质激素诱导的分支和识别相关基因.

主要成果:

转录组分析确定了与对照组相比和对5ARI治疗的反应中,BPH中显著的差异表达基因 (DEGs).
分解分析揭示了S-BPH细胞组成的变化,包括瘤细胞,NK细胞,纤维细胞和光细胞的增加.
在3D培养中使用葡萄糖皮质激素治疗诱导了与前列腺形态发生相关的DEGs,在BPH和3D培养模型之间确定了重叠的途径,包括IL-6和AP-1信号.

结论:

对BPH组织和3D有机体培养的基因表达分析确定了重新激活的前列腺发育途径.
这些发现提供了对BPH医学治疗不响应背后的机制的见解.
已识别的途径代表了BPH和下泌尿道症状 (LUTS) 的潜在新型治疗点.

关键词:

这是一种三维有机物体.良性前列腺增生症 (BPH) 是一种基因路径分析分析较低的尿路症状 (LUTS)

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