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

BACKGROUND: Kallikrein-related peptidase 5 (KLK5) is a secreted trypsin-like protease of the KLK family, encoded by the KLK5 gene. KLK5 has been found to cleave various extracellular matrix components, as well as to activate several other KLK proteases, triggering the stimulation of tissue microenvironment proteolytic cascades. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.