Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Jamie Randall, Allison L. Hunt, Aratara Nutcharoen, Laura Johnston, Safae Chouraichi, Hongkun Wang, Arthur Winer, Raymond Wadlow, Jasmine Huynh, Justin Davis, Brian Corgiat, Nicholas W. Bateman, John F. Deeken, Emanuel F. Petricoin, Thomas P. Conrads, Timothy L. Cannon
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引用次数: 0

Abstract

Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2Total, HER2Y1248, and HER3Y1289. RPPA analysis revealed significant levels of HER2Total in PDAC patients at abundances comparable to HER2-positive (IHC 3+) and HER2-low (IHC 1+ /2+ , FISH−) breast cancer tissues, for which HER2 screening is routinely performed. These data support a critical unmet need for routine clinical evaluation of HER2 expression in PDAC patients and examination of the utility of HER2-directed antibody–drug conjugates in these patients.
PDAC 肿瘤中 HER2 蛋白表达的定量蛋白质组分析
在美国,转移性胰腺腺癌(PDAC)是导致癌症相关死亡的第三大原因,5 年生存率仅为 11%,因此有必要确定新的治疗范例。研究人员收集了PDAC、乳腺癌和其他实体瘤恶性肿瘤患者的肿瘤组织标本,并使用激光显微切割(LMD)技术富集了肿瘤细胞。对富集的肿瘤细胞裂解液进行反相蛋白质阵列(RPPA)分析,以量化 32 种蛋白质/磷蛋白生物标记物面板,其中包括已知的抗癌药物靶点和/或癌症相关的总蛋白和磷酸化蛋白,包括 HER2Total、HER2Y1248 和 HER3Y1289。RPPA分析显示,PDAC患者体内的HER2Total含量明显高于HER2阳性(IHC 3+)和HER2低(IHC 1+ /2+ ,FISH-)乳腺癌组织,而HER2筛查是乳腺癌组织的常规筛查项目。这些数据支持了对 PDAC 患者中 HER2 表达进行常规临床评估以及检查 HER2 靶向抗体药物共轭物在这些患者中的效用的关键需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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