Konishi Hirotaka, Ichikawa Daisuke, Yamamoto Yusuke, Arita Tomohiro, Shoda Katsutoshi, Hiramoto Hidekazu, Hamada Junichi, Itoh Hiroshi, Fujita Yuji, Komatsu Shuhei, Shiozaki Atsushi, Ikoma Hisashi, Ochiai Toshiya, Otsuji Eigo
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Surgery, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Cancer Sci. 2016 Feb;107(2):149-54. doi: 10.1111/cas.12854. Epub 2016 Feb 9.
Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC.
近期研究表明，转移相关的肺腺癌转录本1（MALAT1）在多种人类实体癌中均有过表达，然而，其在肝细胞癌（HCC）患者血浆中的作用尚不清楚。本研究旨在探讨血浆MALAT1水平在HCC患者中的意义。收集了术前HCC患者、肝病患者及健康对照者的血浆样本，以及HCC患者和伴有肝转移的结直肠癌患者的组织样本。检测了血浆和组织中的MALAT1水平。HCC患者血浆MALAT1水平逐渐且显著高于肝病患者，肝病患者又高于健康对照者。MALAT1在HCC组织中的表达略高于配对的癌旁肝组织，但差异不显著。20例HCC患者癌旁肝组织中MALAT1的表达显著高于13例结直肠癌患者正常肝组织中的表达。相反，乙型肝炎感染的HCC患者血浆MALAT1水平显著降低，而乙型肝损伤或肝硬化患者血浆MALAT1水平显著升高。在对HCC患者和肝病患者进行的受试者工作特征曲线分析中，血浆MALAT1的截断值为1.60，曲线下面积为0.66。血浆MALAT1水平与甲胎蛋白或维生素K缺乏诱导蛋白II无关，而联合MALAT1、甲胎蛋白和维生素K缺乏诱导蛋白II检测HCC的敏感性和特异性分别为88.6%和75%。总之，血浆MALAT1水平与肝损伤相关，对预测HCC的发生具有临床应用价值。
