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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，预后较差。 24 例接受 CDDP/5FU 治疗的肝细胞癌 (HCC) 患者。该化疗持续 5 天，停药 2 天，并至少重复 4 周。 24 名患者中有 10 名对这种疗法有反应。通过免疫组织化学测定Nm23-H1蛋白表达。 10 名应答者中有 8 名 nm23-H1 阳性（> 50% 的 HCC 具有 nm23-H1 阳性），而 14 名无应答者中有 5 名 nm23-H1 阴性。这一结果表明 nm23-H1 表达可能是 CDDP/5FU 化疗效果的有用标记。(2) 我们研究了来自训练组的组织样本中的信使 RNA 表达谱，该训练组包括 33 名 HCC 患者，其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，通过 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，我们在 27 名新登记的 HCC 患者的盲法数据集上比较了我们的系统与支持向量机（基于 SVM 的系统）的预测系统的预测性能。在训练组和盲法组中，分别有 12 名 (36%) 和 8 名 (30%) 患者在治愈性手术后 1 年内出现早期肝内复发。我们的系统在盲法组的 27 个样本中，正确预测了 25 个样本（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 的系统在盲法组中只有 16 例 (60%) 正确预测了早期肝内复发或不复发，结果产生的 PPV 仅为 38%，NPV 为 79%。我们的系统可以比基于 SVM 的系统更准确地预测个体 HCC 患者的早期肝内复发或不复发，这表明我们的系统可以作为表征 HCC 转移潜力的新工具。