Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

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

doi:10.1186/s12014-024-09476-7

Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Letter › peer-review

2 Scopus citations

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 HER2^Total, HER2^Y1248, and HER3^Y1289. RPPA analysis revealed significant levels of HER2^Total 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.

Original language	English
Article number	24
Journal	Clinical Proteomics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12014-024-09476-7
State	Published - Dec 2024
Externally published	Yes

Keywords

HER2
Laser microdissection
Pancreatic adenocarcinoma
Proteomics

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10.1186/s12014-024-09476-7

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Randall, J., Hunt, A. L., Nutcharoen, A., Johnston, L., Chouraichi, S., Wang, H., Winer, A., Wadlow, R., Huynh, J., Davis, J., Corgiat, B., Bateman, N. W., Deeken, J. F., Petricoin, E. F., Conrads, T. P., & Cannon, T. L. (2024). Quantitative proteomic analysis of HER2 protein expression in PDAC tumors. Clinical Proteomics, 21(1), Article 24. https://doi.org/10.1186/s12014-024-09476-7

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title = "Quantitative proteomic analysis of HER2 protein expression in PDAC tumors",

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.",

keywords = "HER2, Laser microdissection, Pancreatic adenocarcinoma, Proteomics",

author = "Jamie Randall and Hunt, {Allison L.} and Aratara Nutcharoen and Laura Johnston and Safae Chouraichi and Hongkun Wang and Arthur Winer and Raymond Wadlow and Jasmine Huynh and Justin Davis and Brian Corgiat and Bateman, {Nicholas W.} and Deeken, {John F.} and Petricoin, {Emanuel F.} and Conrads, {Thomas P.} and Cannon, {Timothy L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1186/s12014-024-09476-7",

language = "English",

volume = "21",

journal = "Clinical Proteomics",

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T1 - Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

AU - Randall, Jamie

AU - Hunt, Allison L.

AU - Nutcharoen, Aratara

AU - Johnston, Laura

AU - Chouraichi, Safae

AU - Wang, Hongkun

AU - Winer, Arthur

AU - Wadlow, Raymond

AU - Huynh, Jasmine

AU - Davis, Justin

AU - Corgiat, Brian

AU - Bateman, Nicholas W.

AU - Deeken, John F.

AU - Petricoin, Emanuel F.

AU - Conrads, Thomas P.

AU - Cannon, Timothy L.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

KW - HER2

KW - Laser microdissection

KW - Pancreatic adenocarcinoma

KW - Proteomics

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U2 - 10.1186/s12014-024-09476-7

DO - 10.1186/s12014-024-09476-7

M3 - Letter

AN - SCOPUS:85188105155

SN - 1542-6416

VL - 21

JO - Clinical Proteomics

JF - Clinical Proteomics

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ER -

Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

Abstract

Keywords

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