title: Cell-surface markers for colon adenoma and adenocarcinoma.
abstract: Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Kamini
authors.initials: K
authors.lastname: Sewda
authors.affiliation: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Department of Molecular Genomics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Enkemann
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Binglin
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Tissue Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Lopez
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Wojtkowiak
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Valerie E
authors.initials: VE
authors.lastname: Stark
authors.affiliation: Department of Diagnostic Imaging, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Morse
authors.affiliation: Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.affiliation: Division of Gastroenterology and Hepatology, SUNY Health Sciences Center at Brooklyn, Brooklyn, NY 11203, USA.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Vignesh
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Morse
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: cell surface targets; colorectal cancer; expression profiling; immunohistochemistry; screening