| 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
|
| 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) |
