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综合分析人类表皮生长因子受体2通过DNA,mRNA和蛋白质在各种恶性瘤

Akram Mesleh Shayeb¹, Razelle Kurzrock^2,3, Jacob J Adashek⁴

¹Department of Hematology/Oncology, University of California San Diego, San Diego, CA.

JCO precision oncology

|July 12, 2023

概括

这项研究显示,在各种癌症中,人类表皮生长因子受体2 (HER2) 表达和放大显著变化. 综合测试突出了基因组,mRNA和蛋白质水平之间的差异,影响了抗HER2治疗决策.

科学领域:

在瘤学瘤学.
分子诊断学分子诊断学
基因组学就是基因组学.

背景情况:

人类表皮生长因子受体2 (HER2) 表达是抗HER2治疗反应的关键预测因子.
最近的发现表明,即使是低HER2表达性乳腺癌也可以从特定疗法中受益.
关于HER2转录基因 (mRNA) 表达及其与基因组和蛋白质分析的比较的理解有限.

研究的目的:

在不同癌症类型中使用基因组 (拷贝数变异,CNV),转录组 (mRNA) 和蛋白质 (免疫组织化学,IHC) 分析来比较HER2状态.
调查HER2测试结果的变化和差异.
评估不同HER2测试方式的临床影响.

主要方法:

使用了临床级测定,包括CNV的下一代测序 (NGS),mRNA的定量逆转录聚合酶链反应 (qRT-PCR) 和蛋白质的IHC.
在5305种不同类型的癌症中进行了多机构的HER2测试.
分析了723名患者的所有三个测定 (CNV,mRNA,IHC) 的结果,并检查了结果不一致的特定病例.

主要成果:

总体而言,4.1%的癌症显示HER2放大 (NGS),33.3%的mRNA过度表达,9.3%的IHC阳性.
在所有三种测试的患者中,所有测试中只有7.5%的患者呈阳性,而62.8%的患者呈阴性.
观察到显著的差异,其中20%的患者单独表现出mRNA过度表达 (阴性CNV和IHC).
两个接受HER2向治疗的患者实现了反应,其中一个仅具有HER2 mRNA阳性.

结论:

在使用综合测定 (CNV,mRNA,IHC) 的各种癌症中,在HER2表达和放大方面表现出显著的可变性.
突出了HER2放大和过度表达之间的不一致模式的出现.
强调需要进一步评估这些模式,因为针对HER2的治疗指示扩大.

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