Lewisy抗原和整合素α、β1、αv、β3在上皮性卵巢癌中的表达及其与耐药和预后的关系

摘要

目的：探讨 Lewis y 抗原和整合素α5、β1、αv、β3在上皮性卵巢癌中表达及其与化疗耐药和患者预后的关系。方法：应用免疫组化方法检测 Lewis y 抗原和整合素α5、β1、αv、β3在92例上皮性卵巢癌中的表达，分析上述指标与临床病理参数及预后之间的关系。结果：卵巢癌耐药组中的 Lewis y 及整合素α5、β1、αv、β3的阳性表达明显高于敏感组，且整合素α5、β1、αv、β3的表达与 Lewis y 存在正相关；逻辑回归单元分析发现FIGO 晚期、淋巴结转移、残余病灶＞1cm 和 Lewis y、整合素α5、β1、αv、β3的高表达与卵巢癌化疗耐药相关，逻辑回归多元分析发现 FIGO 晚期和 Lewis y、整合素α5和β1的高表达是与耐药相关性最强的独立因子；Cox生存分析发现 Lewis y 及整合素β1的高表达提示更短的总体生存时间（OS）和无瘤生存时间（PFS）。结论：Lewis y 抗原及整合素α5、β1、αv、β3可以用于卵巢癌化疗耐药的预测，Lewis y 和整合素β1的阳性高表达提示着患者更差的预后，其中 Lewis y 的效能最强。%Objective:To investigate the expressions of Lewis y antigen and integrins α5,β1,αv,β3 in patients with epithelial ovarian cancer (EOC)and their correlations with drug resistance and prognosis.Methods:All 92 EOC patients treated with systemic chemotherapy after cytoreductive surgery were included in this analysis.Patients were divided into two groups,chemotherapy sensitive (n =56)and resistant (n =36).Immunohistochemical (IHC)stai-ning for Lewis y and integrins α5,β1,αv,β3 were conducted on tissues collected during primary debulking surgery. Using multivariate logistic regressions,IHC results were compared to clinical variables and chemotherapy resistance to determine possible correlations.The relationships between IHC expression and progression -free survival (PFS)and overall survival (OS)were analyzed using Kaplan -Meier method and Cox regression analysis.Results:The expres-sions of Lewis y and integrins α5,β1,αv,β3 were significantly higher in the resistant group than that of the sensitive group (all P <0.01)and all the expressions of integrins positively correlated with that of Lewis y (all P <0.05). Univariate logistics analysis revealed that advanced FIGO stage,lymph node metastasis,residual tumor size >1cm as well as high expression of Lewis y,integins α5,β1,αv,β3 were correlated with chemotherapy resistance.Multivariate logistics analysis revealed that high expression of Lewis y,integrin α5 and β1 as well as advanced FIGO stage were in-dependent risk factors for chemotherapy resistance (all P <0.05).Multivariate Cox analysis demonstrated that the following variates were independent predictors of worse PFS and OS survival:high expressions of Lewis y (P =0.013, 0.010),integrin β1 (P =0.031,0.050).Conclusion:The expression of Lewis y and integrins α5,β1,αv,β3 are as-sociated with the development of chemotherapy resistance in EOC.High expression of Lewis y antigen and integrinβ1are independent factors for PFS and OS,in which Lewis y is the most significant.