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Relation between nm23-H1 expression and effect of chemotherapy for hepatocellular carcinoma

nm23-H1表达与肝细胞癌化疗效果的关系

基本信息

批准号：
12671230
负责人：
OKA Masaaki
金额：
$ 2.18万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

(1) Hepatocellular carcinoma (HCC) has a poor prognosis because of the high intrahepatic recurrence rate. 24 Patients with hepatocellular carcinoma (HCC) treated with CDDP/5FU. This chemotherapy was continued for 5 days, discontinued 2 days, and repeated 4 weeks at least. Ten of 24 patients responded to this therapy. Nm23-H1 protein expression was determined by immunohistochemistry. 8 of 10 reponders had nm23-H1 positive (> 50% of HCC having nm23-H1 positive), whereas, 5 of 14 nonresponders had nm23-H1 negative. This result suggest that nm23-H1 expression may be a useful marker for the effect of CDDP/5FU chemotherapy.(2) We investigated messenger RNA expression profiles in tissue specimens from a training set comprising 33 HCC patients with high-density oligonucleotide microarrays representing approximately 6000 genes. We used this training set in a supervised learning manner to construct a predictive system consisting of 12 genes with the Fisher linear classifier. We then compared the predictive performance of our system with that of a predictive system with a support vector machine (SVM-based system) on a blinded set from 27 newly enrolled HCC patients. Early intrahepatic recurrence within 1 year after curative surgery occurred in 12 (36%) and eight (30%) patients in the training and blinded sets, respectively. Our system correctly predicted early intrahepatic recurrence or nonrecurrence in 25 (93%) of 27 samples in the blinded set and had a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 95%. In contrast, the SVM-based system predicted early intrahepatic recurrence or nonrecurrence correctly in only 16 (60%) in the blinded set, and the result yielded a PPV of only 38% and a NPV of 79%. Our system could predict early intrahepatic recurrence or nonrecurrence for individual HCC patients much more accurately than the SVM-based system, suggesting that our system may serve as a new tool for characterizing the metastatic potential of HCC.

(1)肝细胞癌（HCC）由于肝内复发率高，预后差。24例肝细胞癌（HCC）患者接受CDDP/5 FU治疗。该化疗持续5天，停药2天，至少重复4周。24例患者中有10例对该疗法有反应。免疫组化法检测nm 23-H1蛋白表达。10例应答者中8例nm 23-H1阳性（> 50%），而14例无应答者中5例nm 23-H1阴性。提示nm 23-H1表达可作为CDDP/5 FU化疗疗效的一个有用指标。(2)我们研究了组织标本中的信使RNA表达谱的训练集，包括33例肝癌患者的高密度寡核苷酸微阵列代表约6000个基因。我们以监督学习的方式使用这个训练集，用Fisher线性分类器构建了一个由12个基因组成的预测系统。然后，我们比较了我们的系统的预测性能与预测系统与支持向量机（基于SVM的系统）对27名新入组的HCC患者的盲集。治疗性手术后1年内的早期肝内复发发生在12（36%）和8（30%）例患者的培训和盲组，分别。我们的系统正确预测了27个样本中的25个（93%）的早期肝内复发或不复发，阳性预测值（PPV）为88%，阴性预测值（NPV）为95%。相比之下，基于SVM的系统在盲法组中仅在16例（60%）中正确预测了早期肝内复发或不复发，结果得到的PPV仅为38%，NPV为79%。我们的系统可以预测早期肝内复发或不复发的个别肝癌患者更准确地比SVM为基础的系统，这表明我们的系统可以作为一个新的工具来表征肝癌的转移潜力。