Diamandis Eleftherios P, Borgoño Carla A, Scorilas Andreas, Harbeck Nadia, Dorn Julia, Schmitt Manfred
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Clin Biochem. 2004 Sep;37(9):823-9. doi: 10.1016/j.clinbiochem.2004.04.009.
Human kallikrein 11 (hK11) is a secreted serine protease, highly expressed in hormonally regulated tissues, including the prostate and the ovary. Our preliminary studies indicate that hK11 may represent a diagnostic and prognostic biomarker for ovarian cancer. The aim of the present study was to examine the prognostic value of hK11 expression in ovarian tumors.
Using our established immunofluorometric assay, hK11 levels were quantified (ng per mg of total protein) in 134 ovarian tumor extracts and correlated with various clinicopathological variables and outcome [progression-free survival (PFS), overall survival (OS)], over a median follow-up period of 42 months.
hK11 concentration in ovarian tumor cytosols ranged from 0 to 155 ng/mg of total protein, with a median of 1.45 ng/mg. An optimal cutoff value of 6.3 ng/mg was selected to categorize tumors as hK11-positive or negative. hK11-positive tumors were most often of early stage (Stage I/II) and grade (G1/G2) (P < 0.05). Univariate analysis revealed that patients with hK11-positive tumors had a significantly longer PFS (HR of 0.39, P = 0.005) and OS (HR of 0.44, P = 0.033). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of PFS (HR of 0.47, P = 0.042). Kaplan-Meier survival curves further confirmed that women with hK11-positive tumors have longer PFS and OS (P = 0.003 and P = 0.028, respectively). Also, a weak positive correlation was found between the expression levels of tissue hK11 and tissue CA125 (rs = 0.508; P < 0.001).
These results further validate our initial findings that hK11 is an independent marker of favorable prognosis in ovarian cancer patients.
人激肽释放酶11（hK11）是一种分泌型丝氨酸蛋白酶，在包括前列腺和卵巢在内的激素调节组织中高表达。我们的初步研究表明，hK11可能是卵巢癌的一种诊断和预后生物标志物。本研究的目的是检测hK11表达在卵巢肿瘤中的预后价值。
使用我们建立的免疫荧光测定法，对134份卵巢肿瘤提取物中的hK11水平（每毫克总蛋白中的纳克数）进行定量，并在中位随访期42个月内，将其与各种临床病理变量及预后[无进展生存期（PFS）、总生存期（OS）]进行关联分析。
卵巢肿瘤细胞溶质中的hK11浓度范围为0至155纳克/毫克总蛋白，中位数为1.45纳克/毫克。选择6.3纳克/毫克的最佳临界值将肿瘤分为hK11阳性或阴性。hK11阳性肿瘤最常处于早期（I/II期）和低级别（G1/G2）（P<0.05）。单因素分析显示，hK11阳性肿瘤患者的PFS显著更长（风险比为0.39，P=0.005），OS也显著更长（风险比为0.44，P=0.033）。Cox多因素分析表明，hK11是PFS的独立预后指标（风险比为0.47，P=0.042）。Kaplan-Meier生存曲线进一步证实，hK11阳性肿瘤的女性患者具有更长的PFS和OS（分别为P=0.003和P=0.028）。此外，还发现组织hK11和组织CA125的表达水平之间存在弱正相关（rs=0.508；P<0.001）。
这些结果进一步验证了我们最初的发现，即hK11是卵巢癌患者预后良好的独立标志物。
