2003 年度実績報告書

網羅的SAGE解析とGICHIP開発による消化管癌の分子病態解明と診断応用

研究課題

研究課題/領域番号	15390116
研究機関	広島大学
研究代表者	安井弥広島大学, 大学院・医歯薬学総合研究科, 教授 (40191118)
研究分担者	大上直秀広島大学, 大学院・医歯薬学総合研究科, 助手 (60346484) 伊藤玲子広島大学, 大学院・医歯薬学総合研究科, 助手 (30283790) 中山宏文広島大学, 大学院・医歯薬学総合研究科, 助教授 (50253068)
キーワード	SAGE解析 / 消化管癌 / 分子病態 / GICHIP / 診断応用 / 胃癌 / Ex-STOMACHIP / 遺伝子多型
研究概要	SAGE法を用いた消化管癌における網羅的遺歩子発現解析の内、まず、5種類の胃癌についてSAGE解析を行い、38,903個のユニークtagを含む137,706発現tagを同定しNCBIのdatabaseに登録・公開した(GEO accession number : GSE545)。胃癌と正常胃粘膜との比較において特に発現の異なる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遺伝子として、APOC1,CEACAM6,YF13H12が抽出された。また、SAGE database中の15種類の正常組織libraryとの比較及びRT-PCR法により、少なくとも4個の新規胃癌特異的発現遣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・進展に関連する既知の遺伝子及び薬剤感受性のマーカー遣伝子を合わせた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。現在、SAGE法により食道癌の遺伝子発現プロファイルを解析中であり、大腸癌は準備中である。今後、多数症例を対象に発現解析を行い、発癌、浸潤、転移、予後情報との関連を検討する予定である。尚、遺伝子多型解析用SNP-GICHIPによる症例対象研究に備えて約500例の血液DNA及び正常組織DNAを収集し、HER2やMMP-1などの既知遺伝子については、多型と発癌や進展のリスクとの関連を明らかにした。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Oue N: "Gene expression profile of gastric carcinoma : Identification of genes and tags potentially involved in invasion, metastasis and carcinogenesis by serial analysis"Cancer Res. (印刷中). (2004)
[文献書誌] Oshimo Y: "Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma"Int J Cancer. (印刷中). (2004)
[文献書誌] 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)
[文献書誌] Ito R: "Expression of Cb1 linking with EGFR system is associated with tumor progression and poor prognosis of human gastric carcinoma"Virchow Arch. (印刷中). (2004)
[文献書誌] Yasui W: "Histone acetylation and gastrointestinal carcinogenesis"Ann NY Acad Sci. 983. 220-231 (2003)
[文献書誌] Ito R: "Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma"Virchow Arch. 442. 118-123 (2003)
[文献書誌] Oue N: "Expression of the TSP-1 gene and its association with promoter hypermethylation in gastric carcinomas"Oncology. 64. 423-429 (2003)
[文献書誌] 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)
[文献書誌] Ito R: "Expression of osteoprotegerin correlates with aggressiveness and poor progrnosis of gastric carcinoma"Virchow Arch. 443. 146-151 (2003)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Matsumura S: "The promoter methylation status of the DNA repair gene O6-methylguanine-DNA methyltransferase in ulcerative colitis"Virchow Areh. 443. 518-523 (2003)
[文献書誌] 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)
[文献書誌] Tanimoto K: "Hypoxia-inducible factor-1{alpha} polymorphisms associated with enhanced transactivation capacity, implying clinical significance"Carcinogenesis. 24. 1779-1783 (2003)
[文献書誌] 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)
[文献書誌] Kuniyasu H: "Helicobacter pylori infection is closely associated with telomere reduction in gastric mucosa"Oncology. 65. 275-282 (2003)
[文献書誌] Kondo T: "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma"Cancer Res. 64. 523-529 (2004)
[文献書誌] Kondo T: "Expression of RhoC is associated with metastasis of gastric carcinomas"Pathobiol. 71. 19-24 (2004)

2003 年度 実績報告書

網羅的SAGE解析とGICHIP開発による消化管癌の分子病態解明と診断応用

研究代表者

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

研究成果

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

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

[文献書誌] 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)

[文献書誌] Ito R: "Expression of Cb1 linking with EGFR system is associated with tumor progression and poor prognosis of human gastric carcinoma"Virchow Arch. (印刷中). (2004)

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

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

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

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

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

[文献書誌] 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)

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

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

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

2003 年度実績報告書

安井弥広島大学, 大学院・医歯薬学総合研究科, 教授 (40191118)