論文 - 詳細
| RRC ID | 38157 |
|---|---|
| 著者 | Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Kokubo K, Kobayashi H, Kim MS, Sidransky D, Watanabe M. |
| タイトル | Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer. |
| ジャーナル | Oncogene |
| Abstract |
HOP homeobox (HOPX) is an unusual homeobox gene encoding three spliced transcript variants, among which the only HOPX-beta promoter harbors CpG islands. The characteristics of its promoter methylation was analyzed using bisulfite sequencing and quantitative-methylation-specific polymerase chain reaction (Q-MSP), and the effects of HOPX expression were also examined. HOPX-beta expression was silenced in all gastric cancer cell lines tested; its expression could be restored by treatment with demethylating agent. On Q-MSP, HOPX-beta hypermethylation (cut-off value of 3.55) was found in 84% (67 out of 80) of primary tumor tissues and 10% (8 out of 80) of the corresponding normal tissues and could discriminate normal from tumor tissues (P<0.0001). The prognosis of the advanced cases with HOPX-beta hypermethylation was as poor as those with stage IV disease when cut-off value was set at 11.28. This finding was validated in an independent cohort of 90 advanced gastric cancers. The HOPX-beta hypermethylation was also an independent prognostic factor (P=0.029) on multivariate analysis. Exogenous HOPX expression significantly inhibited cell proliferation, colony formation and invasion as well as enhanced apoptosis. Taken together, HOPX-beta promoter methylation is a frequent and cancer-specific event in gastric cancer. Quantitative assessment of HOPX-beta methylation has great clinical potential as a marker of tumor aggressiveness. |
| 巻・号 | 29(22) |
| ページ | 3263-75 |
| 公開日 | 2010-6-3 |
| DOI | 10.1038/onc.2010.76 |
| PII | onc201076 |
| PMID | 20228841 |
| MeSH | Cell Growth Processes / genetics Cell Line, Tumor Cohort Studies CpG Islands DNA Methylation* Gene Expression Regulation, Neoplastic Gene Silencing Genes, Homeobox* Homeodomain Proteins / genetics Humans Immunohistochemistry Neoplasm Invasiveness Prognosis Promoter Regions, Genetic Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology Tumor Suppressor Proteins / genetics |
| IF | 7.971 |
| 引用数 | 44 |
| WOS 分野 | GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | GCIY(RCB0555) Kato III(RCB2088) MKN74(RCB1002) NUGC-4(RCB1939) KE-97(RCB1435) TE-15(RCB1951) |