Preoperative serum microRNA-203 as a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.

Abstract

564 Background: Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. Epithelial-mesenchymal transition (EMT) is a key process that converts polarized immotile epithelial cells into motile, invasive mesenchymal cells, enabling cancer cells to gain stem cell characteristics and an aggressive malignant phenotype such as metastasis. Mir-203 has been shown to directly suppress EMT activators such as ZEB2 and SNAI1/2. However, in spite of the key functional role of miR-203 in cancer metastasis, no previous studies have investigated the clinical significance of miR-203 in patients with CRC. Methods: To examine whether CRCs secret miR-203 in vitro and vivo,we first determined extracellular miR-203 levels in CRC cell culture media. Then, we quantified miR-203 levels in serum from mice with or without metastasis. Next, we investigated miR-203 expression in 58 pairs of primary CRC (pCRC) and corresponding matching liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from CRC patients. Results: HT-29 cells released miR-203 into culture media, which was dependent on cell number and duration of culture. In addition, high serum miR-203 levels were observed in mice with liver metastasis compared to control animals (p=0.0181). Mir-203 expression was significantly upregulated in LM compared to matching pCRC tissues (p=0.0002). Serum miR-203 was significantly upregulated in a tumor stage-dependent manner (p=0.0070), and high miR-203 expression was associated with poor survival in CRC patients (p<0.0001). In contrast to serum, no significant association between miR-203 expression in CRC tissues and clinicopathological findings was recognized. High serum miR-203 expression was an independent risk factor for poor prognosis (HR=2.1) as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2), and distant organs (OR=4.4), respectively. Conclusions: High levels of serum miR-203, which may be derived from several metastatic sites, are associated with poor survival and metastasis, suggesting it is a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.