Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
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DOI：
10.1515/bc.2006.138
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发表时间：
2006-08-01
影响因子：
3.7
通讯作者：
Schmitt, Manfred
中科院分区：
文献类型：
--
作者：
Dorn, Julia;Harbeck, Nadia;Schmitt, Manfred
在上皮性卵巢癌中，高死亡率通常归因于晚期诊断，因为这些肿瘤通常缺乏早期预警症状，但用于预后或治疗反应预测的肿瘤相关生物标志物缺乏。然而，组织激肽肽丝氨酸蛋白酶家族的成员，丝氨酸蛋白酶uPA及其抑制剂PAI-1，与卵巢癌的肿瘤进展有关。因此，我们采用ELISA法检测142例卵巢癌患者原发肿瘤组织标本提取物中的uPA、PAI-1和组织钾化酶hK5-8、10、11和13，并研究这些肿瘤组织相关因子蛋白表达水平之间的关联强度。uPA、PAI-1、hk5、hk8与FIGO分期相关；FIGO III/IV患者组织中hK5表达高于FIGO I/II患者组织。PAI-1和hk5在核分级上差异显著；hK5在G3中的表达高于G1/2。uPA、PAI-1与组织钾化酶之间的相关性较弱。在组织速效系数hK5、6、7、8、10和11的聚类中存在很强的两两相关性，但它们的二元分布依赖于核分级。这些结果支持了几种组织激肽激酶在卵巢癌患者中共表达的观点，证实了这种疾病中存在类固醇激素驱动的组织激肽激酶级联反应。
In epithelial ovarian cancer, the high mortality rate is usually ascribed to late diagnosis, since these tumors commonly lack early-warning symptoms, but tumor-associated biomarkers useful for prognosis or therapy response prediction are in short supply. However, members of the tissue kallikrein serine protease family, the serine protease uPA and its inhibitor PAI-1, are associated with tumor progression of ovarian cancer. Therefore, we used ELISA to determine uPA, PAI-1, and tissue kallikreins hK5-8, 10, 11, and 13 in extracts of 142 primary tumor tissue specimens from ovarian cancer patients and studied the strength of association between protein expression levels of these tumor tissue-associated factors. uPA, PAI-1, hk5, and hk8 were related to FIGO stage; hK5 expression was higher in FIGO III/IV than in FIGO I/II patient tissues. PAI-1 and hk5 differed significantly according to nuclear grading; expression of hK5 was higher in G3 than in G1/2 tumors. Associations between uPA, PAI-1, and the tissue kallikreins were weak. There were strong pairwise correlations within the cluster of tissue kallikreins hK5, 6, 7, 8, 10, and 11, but their bivariate distributions depended on nuclear grading. These results support the notion that several tissue kallikreins are co-expressed in ovarian cancer patients, substantiating the existence of a steroid hormone-driven tissue kallikrein cascade in this disease.