Utility of Kallikrein-Related Peptidases (KLKs) as Cancer Biomarkers

Abstract

Background: The human kallikrein-related peptidase (KLK) family consists of 15 highly conserved serine proteases, which are encoded by the largest uninterrupted cluster of protease genes in the human genome. To date, several members of the family have been reported as potential cancer biomarkers. Although primarily known for their biomarker value in prostate, ovarian, and breast cancers, more recent data suggest analogous roles of KLKs in several other cancers, including gastrointestinal, head and neck, lung, and brain malignancies. Among the proposed KLK cancer biomarkers, prostate-specific antigen (also known as KLK3) is the most widely recognized member in urologic oncology. Content: Despite substantial progress in the understanding of the biomarker utility of individual KLKs, the current challenge lies in devising biomarker panels to increase the accuracy of prognosis, prediction of therapy, and diagnosis. To date, multiparametric KLK panels have been proposed for prostate, ovarian, and lung cancers. In addition to their biomarker utility, emerging evidence has revealed a number of critical functional roles for KLKs in the pathogenesis of cancer and their potential use as therapeutic targets. Summary: KLKs have biomarker utility in many cancer types but individually lack sufficient specificity or sensitivity to be used in clinical practice; however, groups of KLKs and other candidate biomarkers may offer improved performance.

Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

“…Furthermore, dysregulated kallikreinrelated peptidase gene and protein expression has been implicated in cancer (10). In particular, numerous clinical studies have linked the differential expression signatures of KLK genes and proteins to their potential roles as cancer biomarkers (11). Kallikrein-related peptidases may be involved in different stages of cancer growth and progression including cell growth and survival, differentiation, remodeling of extracellular matrix, invasion, angiogenesis, and metastasis (4,10,12).…”

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

“…The association of kallikrein-related peptidases (KLKs) and cancer is well documented in the literature and many KLKs have been shown to be dysregulated in different malignancies (Emami and Diamandis, 2008). Several independent reports have shown that many KLKs are dysregulated in ovarian cancer.…”

Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies

“…Although testicular cancer presents a rising incidence among younger men, the low mortality rates of the disease have not yet encouraged the study of KLK expression. Therefore, a significant prognostic impact has been revealed only for KLK5 expression, as its correlation with lower stages of the disease indicates a more propitious outcome for these patients (Emami and Diamandis, 2008). In the case of renal cell carcinoma, the fact that a large number of patients suffer from advanced stages of the disease, at the time of diagnosis, indicates that prognostic biomarkers capable of clarifying patients' outcome should be the most essential clinical aim.…”

“…Expression analysis of KLK7 in intracranial tumors negatively correlates the mRNA expression levels of this gene with OS probability of patients, whereas KLK7 synthesis has been associated with an enhanced invasive potential of cancer cells, clarifying the unfavorable impact of KLK7 for these tumors (Emami and Diamandis, 2008).…”

“…Methylation of the KLK10 gene has been proposed as an indicator of poor prognosis in both childhood and adult patients, based on its direct association with shorter DFS, compared with non-methylated cases (Emami and Diamandis, 2008).…”