Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients
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DOI:
10.1002/hep.27885
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发表时间:
2015-09-01
期刊:
影响因子:
13.5
通讯作者:
Stein, Ulrike
Stein, Ulrike
中科院分区:
医学1区
文献类型:
--
作者:
Lederer, Andri;Herrmann, Pia;Stein, Ulrike

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肝内胆管癌(ICC)和肝门胆管癌(Klatskin肿瘤)的治愈性治疗仅限于手术切除或原位肝移植。然而,并非所有患者都受益于手术方法,并遭受早期肿瘤复发。对化疗的反应通常很差,直到今天,还没有建立靶向治疗。结肠癌转移相关蛋白1(MACC 1)是最近发现的肝细胞生长因子(HGF)/Met/丝裂原活化蛋白激酶途径的调节剂,其诱导细胞培养物中的增殖、迁移和侵袭,以及小鼠中的转移。MACC 1表达与结肠癌组织中Met表达显著相关,并且对于结肠癌患者远处转移的发生和生存具有高度预后。因此,我们的目的是测量MACC 1,Met和HGF信使RNA的表达在显微切割的肿瘤组织和相应的正常肝组织的156例Klatskin肿瘤(n=76)和ICC(n=80)使用实时定量逆转录聚合酶链反应。我们使用免疫组织化学染色来验证结果。两种肿瘤组织中MACC 1的表达均显著高于相应的正常肝组织(P
Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis-associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n=76) and ICC (n=80) using real-time quantitative reverse-transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P