Hepsin在卵巢上皮癌组织中的表达及其与预后的关系

Over-expression of Hepsin is associated with poor prognosis in epithelial ovarian cancer

目的探讨丝氨酸蛋白酶(Hepsin)过表达与卵巢上皮癌患者预后的相关性。方法采用免疫印迹法检测49例卵巢上皮癌、18例卵巢良性肿瘤和12例正常卵巢组织中Hepsin蛋白的表达,同时采用免疫组化En Vision两步法检测188例卵巢癌石蜡切片Hepsin蛋白的表达,并评估影响无瘤生存时间(PFS)和总生存时间(OS)的高危因素。结果免疫印迹分析显示:在49例卵巢上皮癌患者中,Hepsin高表达36例(73.5%),而正常卵巢组织和良性卵巢组织Hepsin均呈低表达;免疫组化分析显示:在188例卵巢上皮癌患者中,Hepsin高表达128例(68.1%);其平均随访时间为(71.4±0.5)个月;Hepsin高表达者和低表达者5年总生存率分别为24.0%和91.8%(危险比=20.335,95%可信区间:6.011～68.790;P<0.001);Hepsin高表达者和低表达者5年无瘤生存率分别为20.8%和86.8%(危险比=15.604,95%可信区间:5.779～42.133;P<0.001)。结论 Hepsin蛋白过表达是卵巢上皮癌患者的预后影响因素,其有望成为预测卵巢癌预后的标志物。

Objective The purpose of this study was to determine whether Hepsin over- expression is asso- ciated with the prognosis in patients with epithelial ovarian carcinoma. Methods Hepsin expression was evaluated in 12 normal ovary, 18 benign ovarian tumor and 49 ovarian carcinomas specimens by Western blotting; Hepsin expression was detected in 188 ovarian carcinomas specimens by using immunohistochemistry. The follow- up time was （71.4±0.5） months. All the possible risk factors that may influence the progression- free survival time （PFS） and overall survival time （OS） was analyzed. Results Western blotting analysis showed that Hepsin was under- expressed in 12 normal ovary and 18 benign ovarian tumor and over- expressed in 36 ovarian cancer （36/49, 73. 5%）. IHC analysis demonstrated that Hepsin was overexpressed in 122 epithelial ovarian carcinoma （122/188, 68. 1%）. The five- year overall survival （OS） rates for patients with high Hepsin expression and low Hepsin expression were 24. 0% and 91.8% （hazard ratio： 20. 335, 95% CI： 6. 011-68. 790, P〈0. 0001）. The five- year progression- free survival （PFS） rate was 20. 8% for patients in the high- expression group and 86.8% for patients in the low expression group （hazard ratio： 15. 604, 95% CI： 5. 779-42. 133, P〈0. 0001）. Conclusions Hepsin over- expression is a factor in epithelial ovarian carcinoma prognosis , and it may be an important potential biomarker.