Kallikrein-related peptidases in triple negative breast cancer: prognostic value of quantitatively assessed KLK8, KLK10 and KLK11 mRNA expression

Abstract

Background. Triple-negative breast cancer (TNBC) is a breast cancer subtype with poor prognosis and limited targeted therapy options. Multiple KLKs have been described to play key roles in carcinogenesis and metastasis of breast cancer. Purpose. In the present study, the clinical significance of KLK8, KLK10, and KLK11 mRNA expression in tumor tissue of TNBC patients was investigated. Methods. The mRNA expression levels of KLK8, 10, and 11 were quantified by quantitative PCR and their prognostic values were analyzed in a large, well-characterized TNBC cohort (n = 123). Results. Significantly positive correlations were observed between all three KLK mRNA levels indicating coordinate expression of these proteases in TNBC. In univariate analyses, both elevated KLK8, KLK10 as well as all combinations of the three factors (KLK8 + KLK10, KLK8 + KLK11, KLK10 + KLK11, KLK8 + KLK10 + KLK11) were significantly associated with shortened disease-free survival (DFS), while high mRNA levels of KLK11, as well as KLK10 + KLK11 were significantly associated with shortened overall survival (OS). In multivariate Cox regression analyses, KLK10 and all combined factors remained unfavorable independent predictive markers for DFS, while high KLK11 mRNA expression represented an unfavorable independent predictor for OS. Conclusions. Increased KLK8, KLK10, and KLK11 mRNA expression levels are associated with unfavorable prognosis in triple-negative breast cancer. The combination of KLK8 + KLK10 + KLK11 may represent a stronger prognostic biomarker for DFS than KLK8, KLK10, KLK11 alone, or other combinations thereof, whereas KLK11 mRNA expression is an independent prognostic biomarker for OS in TNBC patients.

Inflammatory landscape in Xeroderma pigmentosum patients with cutaneous melanoma

“…As for the KLK10 gene, we found an overexpression in XP patients. Its increased expression in other types of cancers such as triple-negative breast cancer has been associated with poor prognosis 71 .Giving the Fact that KLK10 is also expressed in healthy skin 66 , we could also suspect an association with the development of melanoma which would require further exploration.…”