Open AccessEffect of mi R ‐122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis
Author(s) -
Iino Ichirota,
Kikuchi Hirotoshi,
Miyazaki Shinichiro,
Hiramatsu Yoshihiro,
Ohta Manabu,
Kamiya Kinji,
Kusama Yukiko,
Baba Satoshi,
Setou Mitsutoshi,
Konno Hiroyuki
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12122
Subject(s) - metastasis , colorectal cancer , medicine , primary tumor , cancer research , immunohistochemistry , cancer , oncology , pathology
Control of liver metastasis is an important issue in the treatment of colorectal cancer ( CRC ). Micro RNA s have been shown to be involved in the development of many cancers, but little is known about their role in the process of colorectal liver metastasis. We compared mi RNA expression between primary colorectal tumors and liver metastasis to identify those involved in the process of metastasis. Cancer cells were isolated from formalin‐fixed paraffin‐embedded primary CRC samples and their corresponding metastatic liver tumors in six patients using laser capture microdissection, and mi RNA expression was analyzed using T aq M an mi RNA arrays. The most abundant mi RNA in liver metastasis compared with primary tumors was mi R ‐122. Immunohistochemical analysis revealed that the expression levels of cationic amino acid transporter 1 ( CAT 1 ), a negative target gene of mi R ‐122, were lower in liver metastases than primary tumors ( P < 0.001). Expression levels of CAT 1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis ( P = 0.0333) and tumor stage ( P < 0.0001). In an analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT 1‐low colon cancer had significantly shorter liver metastasis‐free survival ( P = 0.0258) but not overall survival or disease‐free survival. Overexpression of mi R ‐122 and concomitant suppression of CAT 1 in the primary tumor appears to play important roles in the development of colorectal liver metastasis. Expression of CAT 1 in the primary CRC has the potential to be a novel biomarker to predict the risk of postoperative liver metastasis of CRC patients.