Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma

Objective. The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer. Methods. Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed. Results. Interferon-gamma (IFN-gamma) was identified as the target cytokine. Higher levels of IFN-gamma in the ascites of the tumor micro-environment were associated with advanced disease (p = 0.012), higher tumor histological grading (p = 0.004), and sub-optimal surgical status (p = 0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85-4.05, p < 0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01-2.93, p = 0.048) for overall survival (OS) for a 10-fold increase in IFN-gamma concentration in the ascites. An inverse dose-response relationship between IFN-gamma level and survival was also noted (P-trend < 0.001 for DFS and P-trend < 0.042 for OS). Conclusions. Patients with ovarian cancer and higher IFN-gamma expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-gamma levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-gamma. (C) 2013 Elsevier Inc. All rights reserved.