Geng Xiaocong, Babayeva Lamiya, Walch Axel, Aubele Michaela, Groß Eva, Kiechle Marion, Bronger Holger, Dreyer Tobias, Magdolen Viktor, Dorn Julia
Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich (TUM) Germany.
Research Unit Analytical Pathology, Helmholtz Zentrum München Neuherberg, Germany.
Am J Cancer Res. 2020 Jun 1;10(6):1785-1792. eCollection 2020.
In normal physiology, kallikrein-related peptidase 7 (KLK7), together with other members of the kallikrein-related peptidase family, is mainly involved in skin desquamation and keratinization processes. Moreover, expression of KLK7 was shown in various tumor types to be dysregulated and to correlate to patients' survival time. However, there are contradictory reports in breast cancer whether KLK7 represents an unfavorable or favorable prognostic biomarker. In the present study, we examined the prognostic value of KLK7 protein expression in triple-negative breast cancer (TNBC), determined by immunohistochemistry (IHC). A cohort encompassing 133 TNBC specimens, present on tissue microarrays, was analyzed. For quantification of the staining intensity, an automated digital IHC image analysis algorithm was applied. In both Kaplan-Meier and univariate Cox analyses, elevated KLK7 protein levels were significantly linked with prolonged overall survival (OS). In multivariable Cox analysis, addition of KLK7 immunoreactivity scores to the base model (including the clinical parameters age, tumor size, and nodal status) demonstrated that KLK7 protein expression remained as a statistically significant, independent parameter for prolonged OS. These results strongly indicate that KLK7 is a favorable prognostic biomarker in triple-negative breast cancer.
在正常生理状态下,激肽释放酶相关肽酶7(KLK7)与激肽释放酶相关肽酶家族的其他成员一起,主要参与皮肤脱屑和角质化过程。此外,在各种肿瘤类型中,KLK7的表达均显示失调,并与患者的生存时间相关。然而,在乳腺癌中,关于KLK7是不良预后生物标志物还是良好预后生物标志物存在相互矛盾的报道。在本研究中,我们通过免疫组织化学(IHC)检测了三阴性乳腺癌(TNBC)中KLK7蛋白表达的预后价值。分析了组织芯片上的133例TNBC标本队列。为了量化染色强度,应用了一种自动数字免疫组化图像分析算法。在Kaplan-Meier分析和单变量Cox分析中,KLK7蛋白水平升高均与总生存期(OS)延长显著相关。在多变量Cox分析中,将KLK7免疫反应性评分添加到基础模型(包括临床参数年龄、肿瘤大小和淋巴结状态)中表明,KLK7蛋白表达仍然是总生存期延长的一个具有统计学意义的独立参数。这些结果强烈表明,KLK7是三阴性乳腺癌中一个良好的预后生物标志物。