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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients
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Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

机译：结肠癌1中转移相关的是klatskin肿瘤患者生存的独立预后生物标志物

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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<0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P=0.005). Uni- und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease-free survival (DFS; P=0.001 and P<0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389-5.555; P=0.004). Conclusion: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (Hepatology 2015;62:841-850)
机译：肝内胆管癌（ICC）和肝门胆管癌（Klatskin肿瘤）的治疗仅限于手术切除或原位肝移植。但是，并非所有患者都能从外科手术中受益，并且患有早期肿瘤复发。对化学疗法的反应通常较差，并且直到今天，还没有建立针对性的疗法。转移相关的结肠癌1（MACC1）是最近发现的肝细胞生长因子（HGF）/ Met /有丝分裂原激活的蛋白激酶途径的调节剂，可诱导细胞培养中的增殖，迁移和侵袭以及肝癌的转移。老鼠。 MACC1表达与结肠癌组织中的Met表达显着相关，对结肠癌患者远处转移和生存的发生具有高度预后性。因此，我们旨在通过实时定量逆向测量156例Klatskin肿瘤（n = 76）和ICC（n = 80）患者的显微解剖的肿瘤组织和相应的正常肝组织中MACC1，Met和HGF信使RNA的表达。 -转录酶聚合酶链反应。我们使用免疫组化染色来验证结果。两个肿瘤实体的肿瘤组织中的MACC1表达均显着高于相应的正常肝组织中的表达（P <0.001）。有肿瘤复发史的Klatskin肿瘤患者的MACC1表达明显高于无肿瘤复发的患者（P = 0.005）。统一的多元生存分析表明，MACC1高的克拉斯金肿瘤患者的总生存期（OS）和无病生存期明显缩短（DFS;分别为P = 0.001和P <0.001）。多元分析证实，MACC1是Klatskin肿瘤患者总体生存的独立因素（危险比：2.777; 95％置信区间：1.389-5.555; P = 0.004）。结论：我们的研究确定MACC1是Klatskin肿瘤患者OS和DFS的高度预后生物标志物。 MACC1表达可能成为重要的诊断工具，可能成为靶向治疗的候选药物。 （肝病2015; 62：841-850）

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