Kallikrein-related peptidase 6 (<italic>KLK6</italic>) expression differentiates tumor subtypes and predicts clinical outcome in breast cancer patients.

Novel molecular markers that address the heterogeneity of breast cancer (BC) and provide meaningful prognostic information for BC patients are needed. Kallikrein-related peptidase 6 (<italic>KLK6</italic>) is aberrantly expressed and functionally implicated in BC and, like other members of the KLK family, may prove a useful molecular tool for clinical management. Our objective was to assess, for the first time, the clinical relevance of <italic>KLK6</italic> mRNA expression in BC. Total RNA was isolated from 165 breast tumors, as well as 100 adjacent non-cancerous tumor specimens. After cDNA synthesis, and following quality control, quantitative real-time PCR for <italic>KLK6</italic> expression analysis took place. Receiver operating characteristic curves were constructed in order to assess the ability of <italic>KLK6</italic> mRNA expression levels to differentiate between molecular BC subtypes. Survival analyses, using DFS as endpoint, were performed at the univariate and multivariate levels. Publicly available BC databases and online survival analysis tools were used to validate our findings. A significant downregulation of <italic>KLK6</italic> mRNA expression was observed in BC tissue sections compared to the non-cancerous component (<italic>P</italic> < 0.001). The expression of <italic>KLK6</italic> is positively associated with tumor grade (<italic>P</italic> = 0.038) and is overexpressed in TNBC and HER2-positive tumors (<italic>P</italic> < 0.001). Aberrant <italic>KLK6</italic> expression predicts the clinical outcome of BC patients in terms of DFS, independently of currently used prognostic markers (HR = 7.11, 95% CI = 1.19-42.45). The differential expression of <italic>KLK6</italic> and its association with unfavorable outcome in BC patients was validated via in silico analyses. Although an independent external cohort is necessary to confirm our findings, we proved for the first time that <italic>KLK6</italic> can provide independent prognostic information for BC patients. [ABSTRACT FROM AUTHOR]