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Comparative Study
. 2005 Aug 15;11(16):6030-9.
doi: 10.1158/1078-0432.CCR-04-2671.

Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells

Aikou Okamoto  1 , Takashi Nikaido, Kazunori Ochiai, Satoshi Takakura, Misato Saito, Yuko Aoki, Nobuya Ishii, Nozomu Yanaihara, Kyosuke Yamada, Osamu Takikawa, Rie Kawaguchi, Seiji Isonishi, Tadao Tanaka, Mitsuyoshi Urashima
Affiliations
Comparative Study

Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells

Aikou Okamoto et al. Clin Cancer Res. .

Abstract

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.

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