Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Gynecol Oncol. 2013 Oct;131(1):63-8. doi: 10.1016/j.ygyno.2013.07.105. Epub 2013 Aug 1.
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.
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.
Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ 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-γ concentration in the ascites. An inverse dose-response relationship between IFN-γ level and survival was also noted (Ptrend<0.001 for DFS and Ptrend<0.042 for OS).
Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.
卵巢癌相关腹水是评估宿主免疫系统与肿瘤微环境中癌细胞相互作用的理想材料。本研究旨在探讨腹水选定靶细胞因子的表达水平是否可作为预测卵巢癌患者结局的免疫生物标志物。
采用细胞因子谱试剂盒评估 88 例卵巢癌相关腹水标本，选择靶细胞因子。随后对 144 例总样本进行该靶细胞因子分析。分析靶细胞因子与临床特征的相关性。
鉴定出干扰素-γ（IFN-γ）为靶细胞因子。肿瘤微环境中腹水 IFN-γ水平较高与疾病进展（p=0.012）、肿瘤组织学分级较高（p=0.004）和手术状态不理想（p=0.040）相关。多变量分析显示，腹水 IFN-γ浓度增加 10 倍时，无疾病进展生存（DFS）的调整后危险比（HR）为 2.74（95%置信区间（CI）1.85-4.05，p<0.001），总生存（OS）的 HR 为 1.72（95% CI 1.01-2.93，p=0.048）。IFN-γ水平与生存之间也存在反向剂量反应关系（DFS 的 Ptrend<0.001，OS 的 Ptrend<0.042）。
卵巢癌患者腹水 IFN-γ表达水平较高者 DFS 和 OS 较短。腹水 IFN-γ水平可能是一种预后标志物，也是针对 IFN-γ的免疫治疗的潜在参考指标。
