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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

基本信息

批准号：
15390116
负责人：
YASUI Wataru
金额：
$ 9.79万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390116/
关键词：
SAGE gastrointestinal cancer gastric cancer Ex-STOMACHIP genetic polymorphism CLDN18 CDH17 SNP 分子病態 GICHIP 診断応用

项目摘要

Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without a prior knowledge of the sequence of the gene. We performed on 5 samples of gastric cancer with different histology and stages, and created the largest SAGE libraries in the world, containing a total of 137,706 expressed tags including unique 38,903 tags (GEO accession number GSE 545). By comparing gene expression profiles between gastric cancer and normal gastric mucosa in combination with quantitative RT-PCR,APOC1,CEACAM6, and YF13H12 were found to be frequently overexpressed in gastric cancer, and FUS,CDH17,COL1A1,COL1A2, and APOE were associated with tumor progression. We picked up candidate genes that were detected in our gastric cancer libraries but not in the libraries from various normal tissues, especially important or crucial organs. The expression of these genes was examined in gastric cancers and normal human tissues by quantitative RT-PCR and found that at least 8 genes were specifically expressed in gastric cancers. We have developed custom-made oligo-DNA microarray, called Ex-STOMACHIP, with 475 cDNAs including specific genes identified by our SAGE analysis, known genes related to development and progression of cancer, and marker genes for chemosensitivity. By examining gene expression profiles of 20 gastric cancers, we identified gene clusters which can differentiate tumor stage and histology. Regarding the relation between genetic polymorphism of tumor-related genes and gastric cancer, we have performed case-control and case-case studied using about 500 subjects, and found a significant association with SNPs of HER2 and MMP-1. SNP (G/A) in 5'UTR of the CLDN18, newly identified as down-regulated gene in gastric cancer, was found to affect gastric cancer risk (OR-5.17,95%CI:2.01-13.3).

基因表达系列分析（SAGE）是一种强大的技术，可以在没有基因序列先验知识的情况下以定量的方式对基因表达进行全基因组分析。我们对5个具有不同组织学和分期的胃癌样本进行了研究，并创建了世界上最大的SAGE文库，总共包含137，706个表达标签，其中包括38，903个独特标签（GEO登录号GSE 545）。通过比较胃癌和正常胃粘膜的基因表达谱，结合定量RT-PCR，发现APOC 1，CEACAM 6和YF 13 H12在胃癌中频繁过表达，FUS，CDH 17，COL 1A 1，COL 1A 2和APOE与肿瘤进展相关。我们挑选了在我们的胃癌文库中检测到的候选基因，而在各种正常组织，特别是重要或关键器官的文库中没有检测到。用定量RT-PCR方法检测了这些基因在胃癌和正常组织中的表达，发现至少有8个基因在胃癌中特异表达。我们已经开发了定制的寡聚DNA微阵列，称为Ex-STORAGE IP，具有475个cDNA，包括通过SAGE分析鉴定的特定基因，与癌症发展和进展相关的已知基因，以及化学敏感性标记基因。通过检测20例胃癌的基因表达谱，我们确定了可以区分肿瘤分期和组织学的基因簇。关于肿瘤相关基因的遗传多态性与胃癌的关系，我们对约500名受试者进行了病例对照和病例病例研究，发现HER 2和MMP-1的SNP与胃癌有显著关联。CLDN 18基因是新近发现的胃癌下调基因，其5 'UTR的SNP（G/A）与胃癌发生的危险性相关（OR-5.17，95%CI：2.01-13.3）。