诱导型一氧化氮合酶和环氧化酶-2在卵巢癌中的表达：与临床结局的相关性

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome.

作者信息

Raspollini M R, Amunni G, Villanucci A, Boddi V, Baroni G, Taddei A, Taddei G L

机构信息

Department of Human Pathology and Oncology, University of Florence, Florence, Italy.

出版信息

Gynecol Oncol. 2004 Mar;92(3):806-12. doi: 10.1016/j.ygyno.2003.12.023.

DOI:10.1016/j.ygyno.2003.12.023

PMID:14984945

Abstract

OBJECTIVES

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play a critical role in cancer development. We investigated iNOS and COX-2 expression in relation to clinical outcome in 78 International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian serous carcinoma with a low grade of differentiation (G3).

METHODS

Disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. A multivariate analysis (Cox-proportional hazards models) was used to determine the independent effect of each variable on prognosis. Fisher's exact test was used to analyze the distribution of iNOS and COX-2 expression according to clinical complete response to chemotherapy and to the presence of a brief disease-free interval (< or =12 months).

RESULTS

Overall 60 and 125 months cause-specific survival rates were 32% and 11%, respectively. In univariate analysis, iNOS (P=0.005 and P=0.003, respectively), COX-2 (P=0.002 and P=0.007, respectively), residual disease after surgery (P=0.017 and P=0.032, respectively), and FIGO stage (P=0.008 and P=0.025, respectively) were associated with survival and a disease-free interval. In multivariate analysis (Cox proportional hazards models), the factors that were found to be significantly independent predictors of disease relapse as well as survival were iNOS (P=0.014 and P=0.001, respectively), COX-2 expression (P=0.007 and P=0.029, respectively), and FIGO stage (P=0.026 and P=0.05, respectively). iNOS and COX-2 expressions were correlated with a brief disease-free interval (P=0.001) and clinical complete response to first-line chemotherapy (P=0.038 and P=0.033, respectively).

CONCLUSIONS

The evaluation of iNOS and COX-2 expression may give additional prognostic information concerning the clinical outcome of patients with ovarian carcinoma and may encourage them to select more tailored therapies.

摘要

目的

环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）在癌症发展中起关键作用。我们研究了78例国际妇产科联盟（FIGO）III期低分化（G3）卵巢浆液性癌中iNOS和COX-2表达与临床结局的关系。

方法

采用对数秩检验比较无病生存期和特定病因生存率（Kaplan-Meier法）。多因素分析（Cox比例风险模型）用于确定每个变量对预后的独立影响。Fisher精确检验用于根据化疗的临床完全缓解情况以及无病生存期短暂（≤12个月）来分析iNOS和COX-2表达的分布。

结果

总体而言，60个月和125个月的特定病因生存率分别为32%和11%。单因素分析中，iNOS（分别为P = 0.005和P = 0.003）、COX-2（分别为P = 0.002和P = 0.007）、术后残留病灶（分别为P = 0.017和P = 0.032）以及FIGO分期（分别为P = 0.008和P = 0.025）与生存率和无病生存期相关。多因素分析（Cox比例风险模型）中，被发现是疾病复发以及生存的显著独立预测因素的有iNOS（分别为P = 0.014和P = 0.001）、COX-2表达（分别为P = 0.007和P = 0.029）以及FIGO分期（分别为P = 0.026和P = 0.05）。iNOS和COX-2表达与短暂的无病生存期（P = 0.001）以及一线化疗的临床完全缓解相关（分别为P = 0.038和P = 0.033）。