Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer

Abstract

No ideal serum markers for screening colorectal cancer (CRC) have been identified. The aim of this study was to determine the usefulness of endothelial cell-specific molecule-1 (ESM-1) as a serum marker for CRC. Illumina microarray was carried out to search CRC-related biomarkers. cDNA microarray detected that ESM-1 was one of the overexpressed genes in CRC. Overexpression of ESM-1 mRNA was confirmed in tissues of CRC by RT-PCR and real-time PCR. Immunohistochemical staining showed strong expression of ESM-1 in the cytoplasm of tumor cells. Overexpression of ESM-1 in human serum with CRC was found by Western blot analysis. For quantitative analysis of ESM-1 in serum, we determined the ESM-1 levels in serum specimens using an ELISA kit. We showed that the ESM-1 levels in the serum of patients with CRC were significantly elevated (70.1 ± 29.7 pg/mL) compared to healthy subjects (29.7 ± 14.9 pg/mL). The accuracy, sensitivity, and specificity of ESM-1 for CRC were 0.94, 99%, and 73%, respectively, by receiver operating characteristics curve analysis. The positive predictive value and negative predictive value were 63% and 95%, respectively. The likelihood ratios of a positive or negative test result were 73 and 0.27, respectively. When analyzed with a Cox regression model, a higher serum ESM-1 level (≥76.0 pg/mL) was correlated with poor prognosis. This study suggests that expression of ESM-1 is increased in tissue and serum of CRC patients and that ESM-1 can be used as a potential serum marker for the early detection of CRC.