Abstract 404: Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis.

Abstract

Abstract Background: Control of liver metastasis has been an important issue in the treatment of colorectal cancers. Although microRNA (miRNA) has been shown to be involved in the development of many cancers including colorectal cancers, only few studies have investigated the roles of miRNAs in the process of colorectal liver metastasis. In this study, we compared miRNA expression between primary colorectal cancers and their corresponding liver metastasis to identify miRNAs involved in colorectal liver metastasis and to detect novel molecular markers for prediction of the postoperative prognosis of colorectal cancer patients. Methods: Cancer cells were isolated from formalin-fixed paraffin-embedded (FFPE) tissues of primary colorectal cancers and their corresponding metastatic liver tumors in 6 patients using laser capture microdissection methods. miRNA expression was analyzed using TaqMan miRNA array. Protein levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, in 132 primary colorectal cancers and 22 colorectal liver metastases were analyzed by immunohistochemical staining. Relationship between clinicopathological factors and CAT1 expression levels in 132 primary colorectal cancers were evaluated. Results: miR-122 was the most highly expressed in liver metastasis compared with primary tumor. Immunohistochemical analysis revealed that the expression levels of CAT1 were lower in liver metastases than primary tumors (P <0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P=0.0333) and tumor stage (P <0.0001). In the analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P=0.0258) but not overall survival or disease-free survival. Univariate analysis, for clarifying the risk factors of metachronous colorectal liver metastasis after primary resection, revealed that the 5-year liver metastasis-free survival rate was negatively correlated with the existence of lymph node metastasis and positively correlated with expression levels of CAT1 protein in the primary tumors. Conclusions: Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appear to play important roles in the development of colorectal liver metastasis. CAT1 expression in the primary colorectal cancer has a potential to be a novel biomarker with which to predict the risk of postoperative liver metastasis of the patients with colorectal cancer. Citation Format: Ichirota Iino, Hirotoshi Kikuchi, Shinichiro Miyazaki, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Takanori Sakaguchi, Mitsutoshi Setou, Hiroyuki Konno. Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 404. doi:10.1158/1538-7445.AM2013-404 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.