The research to establish the recurrence predicting system for hepatocellular carcinoma patients by use of genome-wide microarray database and to identify therapeutic molecular targets

利用全基因组微阵列数据库建立肝细胞癌患者复发预测系统并确定治疗分子靶点的研究

• 批准号: 16390377
• 负责人: SATOH Seiji
• 金额: $ 9.15万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390377/
• 关键词: Hepatocellular carcinoma; β-atenin; cDNA microarray; TaqMan PCR; LOH; Recurrence; SIAH1; PEG10; 定量的RT-PCR

Results 1We observed a high frequency of LOH on chromosome 16, which correlated with vascular invasiveness of tumors. We performed deletion mapping of chromosome 16 and then identified SIAH1 and found a correlation between its suppressed expression and progression. It has been shown that SIAH1 functions in the phosphorylation-independent degradation of β-catenin and induces apoptosis and growth arrest. To examine if the effects of SIAH1 over-expression depend on the altered β-catenin signaling pathway, we transferred SIAH1 gene into hepatoma cells. SIAH1 significantly induced growth arrest and apoptosis, despite of accumulation of aberrant β-catenin. SIAH1 interacts with another target protein but β-catenin. Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently over-expressed in HCC and to promote cell proliferation. SIAH1 induces apoptosis and growth arrest in hepatoma cells through different mechanisms.Results 2Through a genome-wide cDNA microarray of hepatocellular carcinomas(HCCs), we identified a number a number of genes associated with tumor progression. Thus, to analyze expression profiles more precisely and establish a predictive system of intrahepatic recurrence after surgery, we performed second screening of 47 HCCs by TaqMan PCR consisting of 120 genes. Then we divided 47 HCCs into two groups. 25 HCCs are for training and 22 HCCs are blinded sets for validation. We identified 27 genes that associated with intrahepatic recurrence within 1 year after curative resection. A predictive score, based on expression profiles of 15 of the genes, correctly predicted the recurrent status in 16 of 22 HCCs in the blinded sets. A positive predictive value was 75% and negative predictive value was 71.4%. Accumulation of such data will make it possible to define the nature of individual tumors, to provide clues for identifying new therapeutic targets, and ultimately to optimize treatment of each patient.

结果1我们在16号染色体上观察到LOH，这与focromosoms 16的血管入口和识别的Siah1相关the EXPRESSION Depend on the altered β-cateninininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininininifabureding, SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 SIAH1 Apoptosis, SIAH1 Interacts with Another Target Protein Butting Study That SIAH1 ALSO REDUCES The Amount of Peg10 Protein, Which Is Known to通过不同的机制在HCC中自由表达并促进细胞增殖精确地建立了手术后的ephip术，我们进行了47个基因的第二次筛选，然后将47个HCC分为两组。在15个基因的索引之后，在盲人的15个基因中，在22个HCC中的复发量为75％。每个患者的治疗。

项目成果

SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and independent mechanisms

SIAH1通过β-catenin降解依赖和独立机制导致肝癌细胞生长停滞和凋亡

• 发表时间: 2007
• 期刊: Oncology Reports (in press)
• 作者: Chiharu Tabata;Hajime Kubo;Rie Tabata;Manabu Wada;Keiichiro Sakuma;Masataka Ichikawa;Shiro Fujita;Tadashi Mio;Michiaki Mishima;Yoshibayashi H
• 通讯作者: Yoshibayashi H

Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.

• DOI: 10.3892/or.14.3.701
• 发表时间: 2005-09
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: K. Obama;Katsuaki Ura;S. Satoh;Yusuke Nakamura;Y. Furukawa