Borgoño Carla A, Kishi Tadaaki, Scorilas Andreas, Harbeck Nadia, Dorn Julia, Schmalfeldt Barbara, Schmitt Manfred, Diamandis Eleftherios P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Clin Cancer Res. 2006 Mar 1;12(5):1487-93. doi: 10.1158/1078-0432.CCR-05-2106.
Human kallikrein 8 (hK8/neuropsin/ovasin; encoded by KLK8) is a steroid hormone-regulated secreted serine protease differentially expressed in ovarian carcinoma. KLK8 mRNA levels are associated with a favorable patient prognosis and hK8 protein levels are elevated in the sera of 62% ovarian cancer patients, suggesting that KLK8/hK8 is a prospective biomarker. Given the above, the aim of the present study was to determine if tissue hK8 bears any prognostic significance in ovarian cancer. Using a newly developed ELISA, hK8 was quantified in 136 ovarian tumor extracts and correlated with clinicopathologic variables and outcome [progression-free survival (PFS); overall survival (OS)] over a median follow-up period of 42 months. hK8 levels in ovarian tumor cytosols ranged from 0 to 478 ng/mg total protein, with a median of 30 ng/mg. An optimal cutoff value of 25.8 ng/mg total protein (74th percentile) was selected based on the ability of hK8 values to predict the PFS of the study population and to categorize tumors as hK8 positive or negative. Women with hK8-positive tumors most often had lower-grade tumors (G1), no residual tumor after surgery, and optimal debulking success (P < 0.05). Univariate and multivariate analyses revealed that patients with hK8-positive tumors had a significantly longer PFS and OS than hK8-negative patients (P < 0.05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK8-positive tumors (P = 0.001 and P = 0.014, respectively). These results indicate that hK8 is an independent marker of favorable prognosis in ovarian cancer.
人组织激肽释放酶8（hK8/神经蛋白酶/卵清蛋白酶；由KLK8编码）是一种受类固醇激素调节的分泌型丝氨酸蛋白酶，在卵巢癌中差异表达。KLK8 mRNA水平与患者预后良好相关，62%的卵巢癌患者血清中hK8蛋白水平升高，这表明KLK8/hK8是一种有前景的生物标志物。鉴于上述情况，本研究的目的是确定组织hK8在卵巢癌中是否具有任何预后意义。使用新开发的酶联免疫吸附测定法（ELISA），对136份卵巢肿瘤提取物中的hK8进行定量，并将其与临床病理变量和预后[无进展生存期（PFS）；总生存期（OS）]进行关联分析，中位随访期为42个月。卵巢肿瘤胞质溶胶中的hK8水平在0至478 ng/mg总蛋白之间，中位数为30 ng/mg。基于hK8值预测研究人群PFS的能力以及将肿瘤分类为hK8阳性或阴性的能力，选择了25.8 ng/mg总蛋白（第74百分位数）作为最佳临界值。hK8阳性肿瘤的女性最常患有低级别肿瘤（G1），术后无残留肿瘤，且肿瘤细胞减灭术成功（P<0.05）。单因素和多因素分析显示，hK8阳性肿瘤患者的PFS和OS显著长于hK8阴性患者（P<0.05）。Kaplan-Meier生存曲线进一步证实，hK8阳性肿瘤女性复发和死亡风险降低（分别为P = 0.001和P = 0.014）。这些结果表明，hK8是卵巢癌预后良好的独立标志物。
