title: Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells.
abstract: OBJECTIVE
  We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Aikou
authors.initials: A
authors.lastname: Okamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nikaido
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ochiai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takakura
authors.forename: Misato
authors.initials: M
authors.lastname: Saito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ishii
authors.forename: Nozomu
authors.initials: N
authors.lastname: Yanaihara
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Rie
authors.initials: R
authors.lastname: Kawaguchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Tadao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D016000:Cluster Analysis; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D011379:Prognosis; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017239:Paclitaxel; D002945:Cisplatin