2003 Fiscal Year Annual Research Report

SAGE法による食道癌・胃癌特異的遺伝子の探索とその発癌、進展、予後における意義

Research Project

Project/Area Number	15026210
Research Institution	Hiroshima University
Principal Investigator	安井弥広島大学, 大学院・医歯薬学総合研究科, 教授 (40191118)
Keywords	胃癌 / 食道癌 / SAGE法 / 進展・予後 / カアスタムアレイ / 臨床疫学
Research Abstract	serial analysis of gene expression(SAGE)法を用いて組織型や悪性度の異なる5種類の胃癌組織の遺伝子発現を解析し、38,903個のユニークtagを含む137,706発現tagを同定した(GEO accession number:GSE545)。胃癌特異的発現遺伝子の抽出のため、胃癌libraryと正常胃粘膜との比較から、特に発現の異なる128tagについてクラスター解析を行い、すべての胃癌で共通して発現が亢進している15tagを抽出した。これらに対応する16遺伝子の発現を定量的RT-PCRで検討したところ、APOC1,CEACAM6,YF13H12が、半数以上の胃癌において過剰発現していた。また、SAGE database中の15種類の正常組織libraryで発現がなく、胃癌では発現している遺伝子を約60個抽出し、RT-PCR法で発現を検討したところ、少なくとも4個の新規胃癌特異的発現遺伝子が見い出された。さらに、早期癌と進行癌、原発巣と転移巣から得られたSAGE libraryの比較から、FUS,CDH17,COL1A1,COL1A2,APOEが悪性度と相関することが確認された。SAGE法で抽出された遺伝子に、胃癌の発生・進展に関する既知の遺伝子、薬剤感受性のマーカー遺伝子を合わせた475遺伝子について、SAGE databaseを基にクラスター解析を行ったところ、胃癌と他の癌との判別ができ、さらに、胃癌の種類や悪性度に対応する遺伝子群が同定できた。これをもとに胃癌の病態解析、遺伝子診断用のカスタムアレイEx-STOMACHIPを作成した。今後、多数の臨床例を対象に発現解析を行い、発癌リスク、進展、予後情報との関連を臨床疫学的に検討する予定である。尚、食道癌については、現在、SAGE法により遺伝子発現プロファイルを解析中である。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Oue N: "Gene expression profile of gastric carcinoma : Identification of genes and tags potentially involved in invasion, metastasis and carcinogenesis by serial analysis of gene expression"Cancer Res. (印刷中). (2004)
[Publications] Oshimo Y: "Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma"Int J Cancer. (印刷中). (2004)
[Publications] Matsumura S: "A single nucleotide, polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer"J Cancer Res Clin Oncol. (印刷中). (2004)
[Publications] Ito R: "Expression of Cbl linking with EGFR system is associated with tumor progression and poor prognosis of human gastric carcinoma"Virchow Arch. (印刷中). (2004)
[Publications] Yasui W: "Histone acetylation and gastrointestinal carcinogenesis"Ann NY Acad Sci. 983. 220-231 (2003)
[Publications] Ito R: "Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma"Virchow Arch. 442. 118-123 (2003)
[Publications] Oue N: "Expression of theTSP-1 gene and its association with promoter hypermethylation in gastric carcinomas"Oncology. 64. 423-429 (2003)
[Publications] Hamai Y: "DNA methylation and histone acetylation status of HLTF gene are associated with reduced expression in gastric carcinoma"Cancer Sci. 94. 692-698 (2003)
[Publications] Ito R: "Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma"Virchow Arch. 443. 146-151 (2003)
[Publications] Kuraoka K: "A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer"Int J Cancer. 107. 593-596 (2003)
[Publications] Abe T: "Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light"Biochem Biophys Res Commun. 310. 1168-1174 (2003)
[Publications] Matsumura S: "The promoter methylation status of the DNA repair gene O6-methylguanine-DNA methyltransferase in ulcerative colitis"Virchow Arch. 443. 518-523 (2003)
[Publications] Oue N: "DNA methylation of multiple genes in gastric carcinoma : association with histological type and CpG island methylator phenotype"Cancer Sci. 94. 901-905 (2003)
[Publications] Tanimoto K: "Hypoxia-inducible factor-1{alpha} polymorphisms associated with enhanced transactivation capacity, implying clinical significance"Carcinogenesis. 24. 1779-1783 (2003)
[Publications] Kitadai Y: "Helicobacter Pylori infection influences expression of genes related to angiogenesis and invasion in human gastric carcinoma cells"Biochem Biophys Res Commun. 311. 809-814 (2003)
[Publications] Kuniyasu H: "Helicobacter pylori infection is closely, associated with telomere reduction in gastric mucosa"Oncology. 65. 275-282 (2003)
[Publications] Kondo T: "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma"Cancer Res. 64. 523-529 (2004)
[Publications] Kondo T: "Expression of RhoC is associated with metastasis of gastric carcinomas"Pathobiol. 71. 19-24 (2004)

2003 Fiscal Year Annual Research Report

SAGE法による食道癌・胃癌特異的遺伝子の探索とその発癌、進展、予後における意義

Principal Investigator

安井 弥 広島大学, 大学院・医歯薬学総合研究科, 教授 (40191118)

Research Products

[Publications] Oue N: "Gene expression profile of gastric carcinoma : Identification of genes and tags potentially involved in invasion, metastasis and carcinogenesis by serial analysis of gene expression"Cancer Res. (印刷中). (2004)

[Publications] Oshimo Y: "Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma"Int J Cancer. (印刷中). (2004)

[Publications] Matsumura S: "A single nucleotide, polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer"J Cancer Res Clin Oncol. (印刷中). (2004)

[Publications] Ito R: "Expression of Cbl linking with EGFR system is associated with tumor progression and poor prognosis of human gastric carcinoma"Virchow Arch. (印刷中). (2004)

[Publications] Yasui W: "Histone acetylation and gastrointestinal carcinogenesis"Ann NY Acad Sci. 983. 220-231 (2003)

[Publications] Ito R: "Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma"Virchow Arch. 442. 118-123 (2003)

[Publications] Oue N: "Expression of theTSP-1 gene and its association with promoter hypermethylation in gastric carcinomas"Oncology. 64. 423-429 (2003)

[Publications] Hamai Y: "DNA methylation and histone acetylation status of HLTF gene are associated with reduced expression in gastric carcinoma"Cancer Sci. 94. 692-698 (2003)

[Publications] Ito R: "Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma"Virchow Arch. 443. 146-151 (2003)

[Publications] Kuraoka K: "A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer"Int J Cancer. 107. 593-596 (2003)

[Publications] Abe T: "Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light"Biochem Biophys Res Commun. 310. 1168-1174 (2003)

[Publications] Matsumura S: "The promoter methylation status of the DNA repair gene O6-methylguanine-DNA methyltransferase in ulcerative colitis"Virchow Arch. 443. 518-523 (2003)

[Publications] Oue N: "DNA methylation of multiple genes in gastric carcinoma : association with histological type and CpG island methylator phenotype"Cancer Sci. 94. 901-905 (2003)

[Publications] Tanimoto K: "Hypoxia-inducible factor-1{alpha} polymorphisms associated with enhanced transactivation capacity, implying clinical significance"Carcinogenesis. 24. 1779-1783 (2003)

[Publications] Kitadai Y: "Helicobacter Pylori infection influences expression of genes related to angiogenesis and invasion in human gastric carcinoma cells"Biochem Biophys Res Commun. 311. 809-814 (2003)

[Publications] Kuniyasu H: "Helicobacter pylori infection is closely, associated with telomere reduction in gastric mucosa"Oncology. 65. 275-282 (2003)

[Publications] Kondo T: "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma"Cancer Res. 64. 523-529 (2004)

[Publications] Kondo T: "Expression of RhoC is associated with metastasis of gastric carcinomas"Pathobiol. 71. 19-24 (2004)

安井弥広島大学, 大学院・医歯薬学総合研究科, 教授 (40191118)