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

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(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.