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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

蛋白多糖和各种糖胺聚糖合成酶和磺基转移酶对患者预后的肿瘤依赖性影响

卷 19, 期 3, 2019

页: [210 - 221] 页: 12

弟呕挨: 10.2174/1568009618666180706165845

价格: $65

摘要

背景:与硫酸化糖胺聚糖(GAG)链相连的小亮氨酸富集的蛋白多糖(SLRP)双糖链蛋白聚糖(BGN)和核心蛋白聚糖(DCN)表现出致癌或肿瘤抑制潜能,这取决于细胞环境和与GAG的关联。 目的:我们假设BGN,DCN及其相关的硫酸软骨素(CS)聚合酶,硫酸皮肤素(DS)差向异构酶和各种硫酸酯酶的结构改变和表达水平可能与肿瘤(亚)类型和患者的存活相关。 方法:我们从cBioPortal和R2 Genomics获得了乳腺癌(BC)和胶质瘤患者的数据集。将CS聚合酶,DS差向异构酶和碳水化合物磺基转移酶(CHST)的结构改变和表达模式与BGN和DCN的表达模式进行比较,并与其临床相关性相关联。 结果:在BC中,没有突变,但在BGN,DCN和CS / DS酶中发现了扩增(0.2-2.1%)和缺失(0.05-0.4%)。相反,在胶质瘤中发现错义和/或截短突变(0.1-0.5%),但扩增率降低(0-1.5%)。与BC相比,结构异常导致BGN,DCN,GAG合成酶和CHST的mRNA表达水平改变。 SLPR,CHSY1,CHST4和CHSY3的突变与胶质瘤预后不良相关,而SLRP,CHSY3,CHST15和DSE缺乏突变和拷贝数变异显示BC存活率增加。 结论:在BC和胶质瘤中发现了BGN和DCN与CHST,CS聚合酶和DS差向异构酶的明显关联。因此,在BC和神经胶质瘤中发现PG和GAG合成酶和CHST的结构改变和表达的独特模式,其具有临床相关性,这可能有助于鉴定高风险患者并开发个性化治疗。

关键词: 蛋白多糖,糖胺聚糖修饰酶,癌症,乳腺癌,神经胶质瘤,预后标志物。

图形摘要

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