We aimed to study
mRNA levels and prognostic impact of all 15 human
kallikrein-related
peptidases (KLKs) and their targets,
proteinase-activated receptors (PARs), in surgically treated
prostate cancer (PCa). Seventy-nine patients with localized grade group 2-4 PCas represented aggressive cases, based on metastatic progression during median follow-up of 11 years. Eighty-six patients with similar baseline characteristics, but no
metastasis during follow-up, were assigned as controls. Transcript counts were detected with nCounter technology. KLK12
protein expression was investigated with immunohistochemistry. The effects of KLK12 and KLK15 were studied in LNCaP cells using RNA interference. KLK3, -2, -4, -11, -15, -10 and -12
mRNA, in decreasing order, were expressed over limit of detection (LOD). The expression of KLK2, -3, -4 and -15 was decreased and KLK12 increased in aggressive
cancers, compared to controls (P < .05). Low KLK2, -3 and -15 expression was associated with short
metastasis-free survival (P < .05) in Kaplan-Meier analysis. PAR1 and -2 were expressed over LOD, and PAR1 expression was higher, and PAR2 lower, in aggressive cases than controls. Together, KLKs and PARs improved classification of metastatic and lethal disease over grade, pathological stage and
prostate-specific antigen combined, in random forest analyses. Strong KLK12 immunohistochemical staining was associated with short
metastasis-free and PCa-specific survival in Kaplan-Meier analysis (P < .05). Knock-down of KLK15 reduced colony formation of LNCaP cells grown on
Matrigel basement membrane preparation. These results support the involvement of several KLKs in PCa progression, highlighting, that they may serve as prognostic PCa
biomarkers.