Oncotarget

Research Papers:

Cell-surface marker discovery for lung cancer

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

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Oncotarget. 2017; 8:113373-113402. https://doi.org/10.18632/oncotarget.23009

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Abstract

Allison S. Cohen1, Farah K. Khalil2, Eric A. Welsh3, Matthew B. Schabath4, Steven A. Enkemann5, Andrea Davis1, Jun-Min Zhou6, David C. Boulware6, Jongphil Kim7,9, Eric B. Haura8 and David L. Morse1,9,10

1Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

2Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

3Biomedical Informatics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

4Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

5Molecular Genomics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

6Biostatistics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

7Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

8Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

9Department of Oncologic Sciences, College of Medicine, University of South Florida, Tampa, FL, USA

10Department 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.


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