Identification of biomarkers for drug-resistant endometriosis using clinical proteomics

Identification of biomarkers for drug-resistant endometriosis using clinical proteomics
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利用临床蛋白质组学鉴定耐药子宫内膜异位症的生物标志物

DOI:
10.1007/s13577-020-00465-0
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发表时间:
2021
期刊:
影响因子:
4.3
通讯作者:
Suzuki Atsushi
Suzuki Atsushi
中科院分区:
生物学3区
文献类型:
--
作者:
Kobayashi Yoichi;Fukutomi Toshiyuki;Mita Shizuka;Watanabe Momoe;Suzuki Atsushi

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地诺孕素(Dienogest,DNG)是一种有效且广泛使用的子宫内膜异位症治疗药物,但在临床上,一部分病例对DNG治疗表现出耐药性。在先前的研究中,DNG对细胞因子和生长因子产生的影响,我们偶然发现,在一个子集的情况下,前列腺囊肿液没有表现出抑制DNG的作用。为了阐明DNG耐药的机制,我们进行了蛋白质组学分析,比较DNG敏感和耐药病例之间的蛋白质表达。基于我们的结果,提取了与中性粒细胞活化标志物(髓过氧化物酶、乳转铁蛋白)、炎症(天青杀素、中性粒细胞明胶酶相关脂质运载蛋白等)、以及反映子宫内膜异位囊肿临床环境的其他生物学过程。在这些蛋白质中,azurocidin(AZU)可能是最令人感兴趣的一种,因为azurocidin是一种切割与卵巢透明细胞癌相关的胰岛素样生长因子-1(IGFBP-1)的蛋白酶。我们建议,在本研究中提取的蛋白质值得进一步调查,在它们的关系,癌的发生。
Dienogest (DNG), is an effective and widely used progestin used in the treatment of endometriosis, yet clinically, a subset of cases show resistance to DNG treatment. During a previous investigation on the effect of DNG of cytokines and growth factor production, we incidentally found that endometriotic cyst fluid did not demonstrate inhibitory effects to DNG in a subset of cases. To clarify the mechanisms of this resistance to DNG, we performed proteomics analysis to compare the protein expression between DNG-sensitive and resistant cases. Based upon our results, several proteins were extracted that relate to neutrophil granulocyte activation marker (myeloperoxidase, lactotransferrin), inflammation (azurocidin, neutrophil gelatinase-associated lipocalin, etc.), and others biological processes reflecting the clinical environment of the endometriotic cyst. Among these proteins, azurocidin (AZU) is perhaps most interesting one as azurocidin is a protease that cleaves insulin-like growth factor-1 (IGFBP-1) associated with clear cell carcinoma of the ovary. We propose that the proteins extracted in the present study warrant further investigation in their relationship to carcinogenesis of endometrioma.
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影响因子: 6.4
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