Primary tumor levels of human tissue kallikreins affect surgical success and survival in ovarian cancer patients
Primary tumor levels of human tissue kallikreins affect surgical success and survival in ovarian cancer patients
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DOI：
10.1158/1078-0432.ccr-06-2482
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发表时间：
2007-03-15
影响因子：
11.5
通讯作者：
Harbeck, Nadia
中科院分区：
文献类型：
--
作者：
Dorn, Julia;Schmitt, Manfred;Harbeck, Nadia
目的：人组织激肽释放酶(HK)家族的蛋白水解物和纤溶酶原激活系统在多种恶性肿瘤的进展中起关键作用。采用双抗体夹心法对142例国际妇产科联合会(FIGO)I~IV级卵巢癌患者原发肿瘤组织提取液中尿激酶型纤溶酶原激活物(UPA)及其抑制物PAI-1、HK5-8、HK10、hK11、hK13的抗原水平进行了检测。结果：72例患者根治术后无肉眼可见的残留肿瘤(RT)，所有患者术后均接受含铂类化疗。有意义的无进展生存(PFS)的显著单变量预测因素是RT(>；0)、FIGO分期(III/IV与I/II/III)、腹水量>；500毫升、结节状态以及PAI-1和uPA之间的差异(按分数排序)。在多因素分析中，不良PFS的显著独立因素是RT[危险比(HR)，4.53]和低hK11分数等级(HR，0.30)。总体生存不良的单变量预测因素是RT、FIGO分期、结节状态、腹水量、核分级以及低HK10和hK13。在多因素分析中，总体生存不良的显著独立因素是RT(HR，7.49)、腹水(HR，1.97)和低HK10(HR，0.196)。我们构建了一个基于腹水[优势比(OR)13.1]、核级别(OR 2.92)、hK6(OR 8.5 4)和hK13(OR 0.14)估计RT概率的多变量评分模型，具有良好的样本内预测性能(接受者操作特征下的面积，0.833)。结论：考虑到根治性手术的风险和好处，这样的评分可以支持术前风险分层，并确定替代治疗策略的候选者。这些结果突出了HKS在卵巢癌不同疾病终点中的不同作用及其支持个体化治疗决定的潜力。
Purpose: Proteolytic factors of the human tissue kallikrein (hK) family and the plasminogen activation system play a key role in tumor progression in various malignancies. We determined antigen levels of urokinase-type plasminogen activator (uPA), its inhibitor PAI-1, and hK5-8, hK10, hK11, and hK13 by ELISA in primary tumor tissue extracts of 142 International Federation of Gynecology and Obstetrics (FIGO) I to IV ovarian cancer patients (median follow-up 41 months).Results: After radical surgery, absence of macroscopically visible residual tumor (RT) was achieved in 72 patients; all patients received postoperative platinum-containing chemotherapy. Significant univariate predictors of poor progression-free survival (PFS) were RT (>0), FIGO stages (III/IV versus I/II/III), ascites volume >500 mL, nodal status, and the difference between PAI-1 and uPA (fractionally ranked). In multivariate analysis, significant independent factors for poor PFS were RT [hazard ratio (HR), 4.53] and low hK11 fractional rank (HR, 0.30). Univariate predictors of poor overall survival were RT, FIGO stages, nodal status, ascites volume, nuclear grade, and low hK10 and hK13. In multivariate analysis, significant independent factors for poor overall survival were RT (HR, 7.49), ascites (HR, 1.97), and low hK10 (HR, 0.196). We constructed a multivariate scoring model estimating RT probability, based on ascites [odds ratio (OR), 13.1], nuclear grade (OR, 2.92), hK6 (OR, 8.54), and hK13 (OR, 0.14), with good in-sample predictive performance (area under receiver operating characteristic, 0.833).Conclusions: In view of risks and benefits of radical surgery, such a score could support preoperative risk stratification and identify candidates for alternative therapeutic strategies. These results highlight the distinct roles of the hKs for different disease end points in ovarian cancer and their potential to support individualized therapy decisions.