Down-regulation of kallikrein-related peptidase 5 (KLK5) expression in breast cancer patients: a biomarker for the differential diagnosis of breast lesions

KLK5 expression levels were quantified in 102 cancerous and benign breast tissue specimens, obtained by randomly chosen patients, using RT-qPCR assay. Subsequently, advanced biostatistics were applied in order to analyze the KLK5 expression profile in the two patients' cohorts and also to evaluate its clinical significance for the discrimination of breast tumors.A statistically significant (p < 0.001) down-regulation of the KLK5 expression levels were observed in the malignant specimens compared to the benign ones. Logistic regression and ROC curve analysis revealed the significant (p < 0.001) and the independent (p < 0.001) value of the KLK5 expression quantification, for the discrimination of the malignant from the benign mammary gland biopsies. Moreover, KLK5 expression levels correlate with the pre-menopausal status (p < 0.005) as well as the ER-negative staining (p = 0.028) of women with breast cancer.The quantification of KLK5 expression in breast tissue biopsies may be considered as a novel and independent biomarker for the differential diagnosis between malignant and benign tumors of the mammary gland.The central role of proteases is widely proven in the complex and multiparametric scene of cancer development and progression. Their abnormal expression and function leads mainly to a deregulated degradation of extracellular matrix (ECM) components, as well as to the activation of several signaling molecules and biochemical pathways. Hence, proteases contribute at first to the creation of a malignant phenotype as well as an impending invasiveness facilitating the spread of the tumor cells. Among the proteases of the human degradome, tissue kallikrein 1 (KLK1) and the kallikrein-related peptidases (KLK2-KLK15) compose a group of 15 conserved secreted serine proteases with trypsin- or chymotrypsin-like activities. They are encoded by 15 structurally homologous genes (KLK1-KLK15), which have been mapped on the 19q13.3-4 chromosomal region. KLKs comprise the larges