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

Proc Amer Assoc Cancer Res, Volume 47, 2006 4506 Purpose: We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. Experimental Design: Using 2 newly established Paclitaxel (PTX)-resistant ovarian cancer cell lines from an original PTX-sensitive cell line and 4 super-sensitive and 4 refractory surgical ovarian cancer specimens from PTX-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 PTX-sensitive samples and PTX-resistant samples with permutation tests, which were common in cell lines and patients’ tumors. Results: Eight of these genes showed reproducible results with the real time reverse transcriptase polymerase chain reaction, of which indoleamine 2, 3-dioxygenase (IDO) 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 IDO 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 IDO screened with the GeneChip was positively associated with PTX resistance and with impaired survival in patients with serous type ovarian cancer.