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

Clin Proteomics. 2024 Mar 20;21(1):24. doi: 10.1186/s12014-024-09476-7.

Authors

Jamie Randall^#¹, Allison L Hunt^#^{2

3}, Aratara Nutcharoen^{1

4}, Laura Johnston¹, Safae Chouraichi¹, Hongkun Wang⁵, Arthur Winer¹, Raymond Wadlow¹, Jasmine Huynh¹, Justin Davis⁶, Brian Corgiat⁶, Nicholas W Bateman^{3

7}, John F Deeken¹, Emanuel F Petricoin⁸, Thomas P Conrads^{2

3}, Timothy L Cannon⁹

Affiliations

¹ Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Dr, Fairfax, VA, 22031, USA.
² Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Rd, Annandale, VA, 22042, USA.
³ Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
⁴ Department of Pathology, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA.
⁵ Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
⁶ Theralink Technologies, Inc., 15000 W 6th Ave, Golden, CO, 80401, USA.
⁷ The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
⁸ Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, 20110, USA.
⁹ Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Dr, Fairfax, VA, 22031, USA. Timothy.Cannon@inova.org.

^# Contributed equally.

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.

Keywords: HER2; Laser microdissection; Pancreatic adenocarcinoma; Proteomics.

Publication types

Letter