Detection of MAGE-4 Protein Sera of Patients with Liver Cirrhosis a useful maker for prediction of hepatocellular carcinoma

在日本，大多数肝细胞癌（HCC）是由长期遭受肝炎病毒感染的肝硬化（LC）患者引起的。为了更好地治疗和护理这些患者，需要开发一种有用的血清标志物来预测HCC。我们之前报道HCC和LC患者血清中MAGE-4蛋白均显著高于对照组。本研究通过测量LC （n=61）患者（作为对照）在8年内至少3次不同时间的血清MAGE-4蛋白水平，探讨了MAGE-4蛋白水平是否有助于预测HCC。在此期间，这些LC患者中分别有28例（46%）观察到HCC。诊断为LICC前，28例HCC患者中有14例（50%）的MAGE-4蛋白呈阳性（>1.15 ng/ml）。33例未被诊断为HCC的LC患者中，只有3例（9%）的MAGE-4蛋白呈阳性。7例和5例患者的MAGE-4蛋白水平分别在HCC诊断前1年和2年呈阳性。6例肝癌患者治疗后MAGE-4蛋白均下降，4例变为阴性。然后，我们对28例诊断为HCC的患者进行了预测HCC危险因素的单验证分析：性别、年龄、scrum AST、AFP值和MAGE-4。AFP水平（> 20 ng/ml） （p=0.02）和MAGE-4蛋白水平（p=0.01）是预测HCC的重要因素。并进行了多变量分析。血清MAGE-4蛋白水平是预测预后最显著的危险因素（p = 0.002）。因此，血清MAGE-4水平是预测LC患者HCC的最佳血清指标。血清MAGE-4的测定可能成为预测LC患者HCC的新工具。

The majority of hepatocellular carcinomas (HCC) in Japan are caused from liver cirrhosis (LC) patients who have long suffered with hepatitis virus infection. Development of a useful serum marker for prediction of HCC is needed for better treatment and care of these patients. We previously reported that the MAGE-4 protein in sera of both HCC and LC patients were significantly higher than those of the control.This study has addressed whether level of MAGE-4 protein is useful for prediction of HCC by measurement of the serum MAGE-4 protein in LC (n=61) patients as a control at least 3 different times within 8 years. HCC was observed in 28 (46%) of these LC patients during this period, respectively. MAGE-4 protein was positive (>1.15 ng/ml) in 14 of 28 HCC patients (50%) before the diagnosis of LICC. And MAGE-4 protein was positive in only 3 of 33 LC patients (9%) who were not diagnosed as HCC. Levels of MAGE-4 protein in 7 or 5 patients were positive one or two year before the time of diagnosis of HCC, respectively. MAGE-4 protein decreased after the treatment of HCC in all the 6 patients tested, and became negative in 4 patients.We then performed the uni-valiated analysis of the predicting risk factors of HCC : gender, age, scrum AST, AFP value and MAGE-4 in 28 patients diagnosed as HCC. AFP level (over 20 ng/ml) (p=0.02) and MAGE-4 protein level (p=0.01) were significant as a factor for prediction of HCC.The multi-variated analysis was also performed. The MAGE-4 protein level in sera was the most significant risk factor for the prediction (p = 0.002).Thus, level of serum MAGE-4 was better that the any other serum markers tested for prediction of HCC in LC patients.Measurement of serum MAGE-4 could be a novel tool for prediction of HCC in LC patients.