| Project/Area Number |
12671230
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKA Masaaki Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70144946)
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| Co-Investigator(Kenkyū-buntansha) |
IIZUKA Norio Yamaguchi University School of Medicine, Lecturer, 医学部, 寄附講座教員 (80332807)
MORI Noahide Yamaguchi University Hospital, Lecturer, 医学部附属病院, 助手 (70325231)
HAZAMA Shoichi Yamaguchi University Hospital, Assistant Professor, 医学部附属病院, 講師 (50253159)
前田 義隆 山口大学, 医学部, 助手 (30291488)
西田 峰勝 山口大学, 医学部・附属病院, 講師 (80243666)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Hepatocellular carcinoma / nm23-H1 / Chemotherapy / Intrahepatic recurrence / Microarray / Immunohistochemical staining / NM23-H1遺伝子 / 肝再発 / 免疫染色 / 肝細胞癌 / テロメラーゼ活性 / RT-PCR |
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| Research Abstract |
(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.
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