Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1 alpha in human colon carcinoma: Impact of ESM-1 on prognosis and its correlation with clinicopathological features

Abstract

Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1) is a potential serum marker for colorectal cancer (CRC), the aim of this study was to clarify the clinicopathological significance of ESM-1 expression in CRC, and to explore the correlation between ESM-1 and HIF-1 alpha in the tumorigenesis of CRC related to hypoxic conditions. ESM-1 mRNA expression was examined in CRC and corresponding normal mucosal tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. This experiment confirmed that ESM-1 levels were high in CRC. We screened the tissue samples of 143 CRC patients. By immunohistochemistry, we determined that the ESM-1 immunoreactivity was significantly correlated with the tumor size, depth of invasion, nodal status, distant metastasis and Dukes' stage, and was an independent prognostic factor for disease recurrence and worse survival outcome (P=0.001). The modulation of ESM-1 under hypoxia was investigated, and it was confirmed that ESM-1 expression was induced by HIF1-alpha and significantly attenuated by small interfering RNA (siRNA) targeting HIF-1 alpha in CRC cells. These results showed that ESM-1 is significantly overexpressed, which is regulated by HIF-1 alpha in CRC patients, and can be used as a potential biomarker and a therapeutic target for CRC.