論文 - 詳細
RRC ID | 38446 |
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著者 | Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K. |
タイトル | Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma. |
ジャーナル | Cancer |
Abstract |
BACKGROUND:The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC). METHODS:ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines. RESULTS:Gene amplification was identified in 12 of 60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with shorter progression-free (P = .0042) and overall (P = .0199) survival. There were nonsignificant trends between high ZNF217 protein expression and poor progression-free (P = .2594) and overall (P = .2199) survival. Multivariate analysis revealed ZNF217 gene amplification to be an independent prognostic factor for progression-free and overall survival after standard platinum agent-based chemotherapy (P = .0339 and P = .031, respectively). Profound growth inhibition and apoptosis were observed in ZNF217 siRNA-treated cancer cells with gene amplification compared with cancer cells with ZNF217 moderate expression without ZNF217 gene amplification or with low ZNF217 expression. CONCLUSION:These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted therapy may benefit OCCC patients with ZNF217 amplification. |
巻・号 | 118(11) |
ページ | 2846-57 |
公開日 | 2012-6-1 |
DOI | 10.1002/cncr.26598 |
PMID | 22139760 |
MeSH | Adenocarcinoma, Clear Cell / genetics* Adenocarcinoma, Clear Cell / mortality Adenocarcinoma, Clear Cell / therapy* Cell Line, Tumor Chromosomes, Human, Pair 20 DNA Copy Number Variations Disease-Free Survival Female Gene Amplification* Gene Expression / drug effects Gene Knockdown Techniques Humans Middle Aged Ovarian Neoplasms / genetics* Ovarian Neoplasms / mortality Ovarian Neoplasms / therapy* Prognosis Trans-Activators / genetics* |
IF | 5.772 |
引用数 | 36 |
WOS 分野 | ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 | JHOC-9(RCB2226) |