Abstract 1156: Cell-surface marker discovery for colorectal cancer

Abstract

Abstract In the United States and Europe, colorectal cancer (CRC) has the second highest mortality rate of all cancers. Early diagnosis allows for treatment and improved survival. Currently, colonoscopy is the standard of care for detection of early-stage CRC, which is an invasive procedure that requires a cathartic bowel preparation and general anesthesia. Consequently, less invasive screening methods are highly desirable. The objective of this study is to develop a targeted molecular imaging technique termed “molecular colonography,” that can non-invasively detect dysplastic and neoplastic colonic lesions with high sensitivity and conspicuity by oral administration of ligand-targeted probes containing image contrast agents followed by clearance and non-invasive colonography with MRI, CT or Fluorescence imaging. The first step in the development of molecular colonography is identification of cell-surface markers for CRC. To accomplish this goal, gene expression profiling of DNA microarray data from 432 adenocarcinomas, 39 adenomas and 16 inflammatory bowel disease; and unaffected patient tissue samples (178 colon, 6 small intestine, 4 stomach, 4 esophagus, 4 trachea, 3 oral mucosa and 3 tonsil) was performed. Data were filtered using a previously compiled list of 3,800 cell surface genes from the NCBI Gene Expression Omnibus database. Of these, 1085 genes were broadly expressed in CRC and were ranked by differential expression in adenomas and adenocarcinomas vs. normal tissues. Six cell-surface markers were identified that are highly and broadly expressed as mRNA in adenomas and adenocarcinomas relative to unaffected tissues: TLR4, GPR56, GRM8, LY6G6D, CLDN1 and SLC01B3. TLR4 and/or GRM8 were shown to be expressed in 100% of the colon adenomas and adenocarcinomas in this dataset. To confirm protein expression, immunohistochemistry of normal (n=15) and CRC (16 adenoma and 60 adenocarcinoma) patient tissue samples and 26 CRC cell lines was performed. All six markers were highly and broadly expressed in adenomas and adenocarcinomas compared to normal colon. Further validations by mRNA (qRT-PCR) and protein expression (Western blot and immunocytochemistry) of these markers were also performed in nine colon tumor cell lines (COLO-205, DIFI, HCT15, HCT116, HT-29, KM12C, Km12SM, SW480 and SW620). Development of specific binding ligands for selected targets is underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1156. doi:1538-7445.AM2012-1156