Br J Cancer:酯酶基因表达水平在多发性骨髓瘤中的预后意义

2021-02-04 xiaozeng MedSci原创

酯酶家族是水解酶超家族的一个子家族,其主要功能为水解酯键。目前已鉴定出许多不同的酯酶,其底物特异性和生物学功能各不相同,且既往研究显示,在癌症中特定酯酶的表达失调。

酯酶家族是水解酶超家族的一个子家族,其主要功能为水解酯键。目前已鉴定出许多不同的酯酶,其底物特异性和生物学功能各不相同,且既往研究显示,在癌症中特定酯酶的表达失调。

因此,酯酶的水解代表了一种有趣的潜在机制,其或可在癌细胞中选择性的激活抗癌药物,同时能够最大程度地减少了对健康细胞和组织的毒性。


既往研究揭示了许多在多发性骨髓瘤(MM)中高频率突变的基因,尽管编码酯酶的基因在其中并不突出,但也反过来表明,酯酶基因的表达调控是通过突变以外的机制所实现的。因此,该研究旨在评估多发性骨髓瘤(MM)中酯酶表达调控的相关生物学意义。

来自FIMM数据集的多发性骨髓瘤样本中的酯酶基因表达谱

在该研究中,研究人员通过芬兰分子医学研究所(FIMM)队列进行基因表达谱分析,评估相关基因组突变,并从新确诊MM(NDMM)患者或复发/难治性MM(RRMM)患者中获取相应的骨髓穿刺物。通过富集CD138+浆细胞并用于RNA测序和分析,以评估基因组突变信息。


研究人员将多发性骨髓瘤研究基金会(MMRF)与MM患者的临床结果与个人遗传档案评估(CoMMpass)数据集联系起来,用于验证FIMM队列的发现。

酯酶表达水平对患者预后的意义

结果显示,共从MM患者(NDMM,n = 56;RRMM,n = 78)中获得了171例骨髓穿刺物(NDMM,n = 56;RRMM,n = 115)。研究人员发现,在MM中特定的酯酶表现出相对较高或较低的表达水平,且特定酯酶(UCHL5、SIAE、ESD、PAFAH1B3、PNPLA4和PON1)的表达水平在NDMM向RRMM演变时显著改变。OVCA2、PAFAH1B3、SIAE和USP4的高表达水平和PCED1B的低表达水平被认为是患者不良预后的指标。


进一步的研究结果显示,MMRF CoMMpass数据集提供了以下的验证:PAFAH1B3和SIAE的较高表达水平和PCED1B的较低表达水平与患者的不良预后相关。


总而言之,该研究结果揭示,随着患者从NDMM向RRMM发展,酯酶基因的表达水平会发生变化。OVCA2、PAFAH1B3、USP4和SIAE的高表达水平和PCED1B的低表达水平是MM患者不良预后的标志物,这些结果也说明了这些酯酶在骨髓瘤发生发展过程中的作用。


原始出处:

Kumari, R., Majumder, M.M., Lievonen, J. et al. Prognostic significance of esterase gene expression in multiple myeloma. Br J Cancer (03 February 2021).

 

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    2021-05-27 jml2009
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    2021-02-05 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2021-02-05 carrotlyl

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