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Cell-surface marker discovery for lung cancer

2017; Impact Journals LLC; Volume: 8; Issue: 69 Linguagem: Inglês

10.18632/oncotarget.23009

1949-2553

Allison S. Cohen, Farah Khalil, Eric A. Welsh, Matthew B. Schabath, Steven A. Enkemann, A. Davis, Jun-Min Zhou, David Boulware, Jongphil Kim, Eric B. Haura, David L. Morse,

Glycosylation and Glycoproteins Research

// Allison S. Cohen 1 , Farah K. Khalil 2 , Eric A. Welsh 3 , Matthew B. Schabath 4 , Steven A. Enkemann 5 , Andrea Davis 1 , Jun-Min Zhou 6 , David C. Boulware 6 , Jongphil Kim 7, 9 , Eric B. Haura 8 and David L. Morse 1, 9, 10 1 Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 2 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 3 Biomedical Informatics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 4 Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 5 Molecular Genomics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 6 Biostatistics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 7 Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 8 Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 9 Department of Oncologic Sciences, College of Medicine, University of South Florida, Tampa, FL, USA 10 Department of Physics, College of Arts and Sciences, University of South Florida, Tampa, FL, USA Correspondence to: David L. Morse, email: David.Morse@moffitt.org Keywords: lung cancer; cell-surface; target biomarker; targeted therapeutics; molecular imaging Received: September 08, 2017 Accepted: November 11, 2017 Published: December 07, 2017 ABSTRACT Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.