Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis.
Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis.
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DOI：
10.1038/bjc.2017.291
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发表时间：
2017-10-24
影响因子：
8.8
通讯作者：
Konno H
中科院分区：
文献类型：
--
作者：
Murakami T;Kikuchi H;Ishimatsu H;Iino I;Hirotsu A;Matsumoto T;Ozaki Y;Kawabata T;Hiramatsu Y;Ohta M;Kamiya K;Fukushima M;Baba S;Kitagawa K;Kitagawa M;Konno H
肿瘤间质在结直肠癌（CRC）转移的发生中发挥重要作用。我们的目的是阐明微小RNA（miRNAs）及其靶基因在结直肠癌间质中肝转移发生中的作用。通过激光捕获显微切割从有或无肝转移的原发性CRC的福尔马林固定、石蜡包埋组织中分离肿瘤间质，并使用TaqMan miRNA阵列分析miRNA表达。根据是否存在同步性肝转移，分层聚类将16例CRC分为两组。组合靶点预测将腱生蛋白C鉴定为miR-198的预测靶点，miR-198是在具有同步肝转移的CRC的肿瘤基质中下调的前10种miRNA之一。139例原发性结直肠癌组织中腱生蛋白C的免疫组化分析显示，腱生蛋白C的高表达与同时发生的肝转移有关（P<0.001）。单变量和多变量分析显示，腱生蛋白C染色强度是预测术后总生存率（P=0.005; n=139）和无肝转移生存率（P=0.001; n=128）的独立预后因素。CRC间质中miRNA的改变似乎形成了一个允许转移的环境，可以提高腱生蛋白C以促进肝转移。原发性CRC间质中的腱生蛋白C有可能成为预测术后预后的新型生物标志物。
Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128). Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
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影响因子：
5.7
作者：
Iino, Ichirota;Kikuchi, Hirotoshi;Konno, Hiroyuki
通讯作者：
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影响因子：
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作者：
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