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Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells.
Okamoto, Aikou; Nikaido, Takashi; Ochiai, Kazunori; Takakura, Satoshi; Saito, Misato; Aoki, Yuko; Ishii, Nobuya; Yanaihara, Nozomu; Yamada, Kyosuke; Takikawa, Osamu; Kawaguchi, Rie; Isonishi, Seiji; Tanaka, Tadao; Urashima, Mitsuyoshi.
Afiliação
  • Okamoto A; Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
Clin Cancer Res ; 11(16): 6030-9, 2005 Aug 15.
Article em En | MEDLINE | ID: mdl-16115948
PURPOSE: We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. EXPERIMENTAL DESIGN: Using two newly established paclitaxel-resistant ovarian cancer cell lines from an original paclitaxel-sensitive cell line and four supersensitive and four refractory surgical ovarian cancer specimens from paclitaxel-based chemotherapy, molecules associated with chemoresistance were screened with gene expression profiling arrays containing 39,000 genes. We further analyzed 44 genes that showed significantly different expressions between paclitaxel-sensitive samples and paclitaxel-resistant samples with permutation tests, which were common in cell lines and patients' tumors. RESULTS: Eight of these genes showed reproducible results with real-time reverse transcription-PCR, of which indoleamine 2,3-dioxygenase gene expression was the most prominent and consistent. Moreover, by immunohistochemical analysis using a total of 24 serous-type ovarian cancer surgical specimens (stage III, n = 21; stage IV, n = 7), excluding samples used for GeneChip analysis, the Kaplan-Meier survival curve showed a clear relationship between indoleamine 2,3-dioxygenase staining patterns and overall survival (log-rank test, P = 0.0001). All patients classified as negative survived without relapse. The 50% survival of patients classified as sporadic, focal, and diffuse was 41, 17, and 11 months, respectively. CONCLUSION: The indoleamine 2,3-dioxygenase screened with the GeneChip was positively associated with paclitaxel resistance and with impaired survival in patients with serous-type ovarian cancer.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Cistadenocarcinoma Seroso / Perfilação da Expressão Gênica / Indolamina-Pirrol 2,3,-Dioxigenase Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Cistadenocarcinoma Seroso / Perfilação da Expressão Gênica / Indolamina-Pirrol 2,3,-Dioxigenase Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article