Functional analysis of gastric cancer-specific genes identified by SAGE data and its clinical implication

SAGE数据鉴定的胃癌特异性基因的功能分析及其临床意义

基本信息

  • 批准号:
    17390104
  • 负责人:
  • 金额:
    $ 9.28万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

The purpose of the study is to identify novel gastric cancer-specific genes through SAGE data analysis and to establish new system of cancer diagnosis oriented towards molecular target therapy. Following results were obtained:1) By comparison between SAGE libraries of gastric cancer (GSE545) and 14 normal organs in combination with RT-PCR, 9 gastric cancer-specific genes (APIN, MIA, MMP-10, DKK4, REGIV, etc.) have been identified.2) By immunostaining, expression of MIA and MMP-10 were correlated with grade of malignancy and poor prognosis. REGIV expression was detected not only in gastric cancer but in colorectal cancer, pancreas cancer and GI carcinoid.3) By ELISA, high levels of REGIV and MMP-10 in sera were detected in 36% and 95% of gastric cancer patients, respectively.4) Through functional analyses, phosphorylation of EGFR and inhibition of caspase-9 were found to participate in apoptosis inhibition by 5-FU. SCP18, whose expression is associated with tumor stage and metastasis, promoted cell invasion by forced expression in gastric cancer cell line.5) Regarding the relation between genetic polymorphism of tumor-related genes and gastric cancer, SNP (G/A) in 5'UTR of the CLDN18, new candidate tumor suppressor of gastric cancer, was found to affect gastric cancer risk (OR-5.17, 95%CI: 2.01-13.3).6) We have developed custom-made oligo-DNA microarray with 207 cDNAs including specific genes identified by SAGE analysis, known genes related to development and progression of cancer, and genes participating in DNA damage response and repair. By examining gene expression profiles of 20 gastric cancers, we identified 23 genes related invasion, nodal metastasis and tumor stage.
本研究旨在通过SAGE数据分析,发现新的胃癌特异性基因,建立面向分子靶向治疗的癌症诊断新体系。结果如下:1)将胃癌SAGE文库(GSE545)与14个正常器官的SAGE文库结合RT-PCR进行比较,鉴定出9个胃癌特异性基因(APIN、MIA、MMP-10、DKK4、REGIV等)。2)免疫染色发现MIA和MMP-10的表达与恶性程度及预后不良相关。REGIV不仅在胃癌中有表达,在结直肠癌、胰腺癌和胃肠道类癌中也有表达。3) ELISA检测胃癌患者血清中REGIV和MMP-10的高表达率分别为36%和95%。4)通过功能分析,发现EGFR的磷酸化和caspase-9的抑制参与了5-FU对细胞凋亡的抑制。SCP18在胃癌细胞系中通过强制表达促进细胞侵袭,其表达与肿瘤分期和转移有关。5)关于肿瘤相关基因遗传多态性与胃癌的关系,发现新的胃癌候选抑癌基因CLDN18的5' utr SNP (G/A)影响胃癌的发生风险(OR-5.17, 95%CI: 2.01-13.3)。6)我们开发了定制的低聚DNA芯片,包含207个cdna,包括SAGE分析鉴定的特定基因,已知的与癌症发生进展相关的基因,以及参与DNA损伤反应和修复的基因。通过检测20例胃癌的基因表达谱,我们发现了23个与侵袭、淋巴结转移和肿瘤分期相关的基因。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes
  • DOI:
    10.1002/ijc.20859
  • 发表时间:
    2005-06-20
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Kitadai, Y;Kodama, M;Chayama, K
  • 通讯作者:
    Chayama, K
DNA methylation profile in differentiated type gastric carcinoma with distinct mucin phenotypes
具有不同粘蛋白表型的分化型胃癌的 DNA 甲基化谱
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Motoshita;J.
  • 通讯作者:
    J.
The diversity of gastric carcinoma : pathogenesis, diagnosis, and therapy
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    上西 紀夫;K. Takubo;K. Mafune
  • 通讯作者:
    上西 紀夫;K. Takubo;K. Mafune
Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression
  • DOI:
    10.1159/000086627
  • 发表时间:
    2005-01-01
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Oue, N;Aung, PP;Yasui, W
  • 通讯作者:
    Yasui, W
DNA demethylation of vascular endothelial growth factor-C is associated with gene expression and its possible involvement of lymphagiogenesis in gastric cancer
血管内皮生长因子-C DNA 去甲基化与基因表达及其可能参与胃癌淋巴管生成有关
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Matsumura S;Mitani Y;Matsumura S.;Matsumura S
  • 通讯作者:
    Matsumura S
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YASUI Wataru其他文献

YASUI Wataru的其他文献

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{{ truncateString('YASUI Wataru', 18)}}的其他基金

nalysis of non-coding RNAs transcribed from ultraconserved regions in digestive tract cancer and its diagnostic and therapeutic application
消化道癌超保守区转录非编码RNA分析及其诊断和治疗应用
  • 批准号:
    24659163
  • 财政年份:
    2012
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Protein processing system-regulating microRNA in gastrointestinal carcinogenesis and its clinical application
蛋白质加工系统——调控microRNA在胃肠道癌变中的作用及其临床应用
  • 批准号:
    22659074
  • 财政年份:
    2010
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Analysis of genes encoding secretory and membrane protein by CAST method and microRNA regulation in esophago-gastric cancer and its clinical application
CAST法及microRNA调控食管胃癌分泌蛋白和膜蛋白基因分析及其临床应用
  • 批准号:
    21390105
  • 财政年份:
    2009
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular characterization of gastrointestinal cancer through serial analysis of gene expression and GICHIP and its diagnostic implication
通过基因表达和 GICHIP 的系列分析进行胃肠癌的分子表征及其诊断意义
  • 批准号:
    15390116
  • 财政年份:
    2003
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Systemic analysis of transcriptome in cancer and precancerous lesion of the esophagus and stomach
食管胃癌及癌前病变转录组的系统分析
  • 批准号:
    13470045
  • 财政年份:
    2001
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The role of inhibitory transcription factor GCF on invasion and metastasis of gastrointestinal cancer and its genetic abnormality
抑制性转录因子GCF在胃肠道肿瘤侵袭转移及遗传异常中的作用
  • 批准号:
    06670192
  • 财政年份:
    1994
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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