Tissue kallikrein (KLK1) and the kallikrein-related peptidase (KLK2-15) genes encode for a subgroup of 15 homologous secreted serine proteases possessing numerous physiological roles, such as the regulation of blood pressure, hormone processing and tissue remodeling. The expression of KLKs is detected in a broad spectrum of human tissues where it has been found to be regulated mainly by steroids hormones. The aberrant expression of KLKs, presented in many human malignancies, highlights the significance of this gene family for early diagnosis, prognosis and monitoring of cancer patients, as it is strongly emphasized by the routine use of PSA (KLK3) for prostate cancer management. Here, we review the presently known data regarding the role of KLKs as cancer biomarkers, giving emphasis on novel information about the subject.

Prostate cancer is the most commonly diagnosed malignancy in male populations in the Western world. The KLK15 gene, the newest member of the kallikrein family, is expressed in the prostate gland. The purpose of this study is the expression analysis and the clinical evaluation of the KLK15 mRNA spliced variants in prostate cancer (CaP) and benign prostatic hyperplasia (BPH) patients. Total RNA was isolated from 104 CaP and BPH tissue specimens. After testing the quality of the RNA, cDNA was produced by reverse transcription, and PCR was performed for the amplification of the KLK15 mRNA transcripts. GAPDH and HPRT genes were used as endogenous controls Our data revealed that mRNA spliced variants of KLK15 were differentially expressed in prostate tissue specimens. Analysis of data showed a statistically significant (P < 0.001) increase in the frequency of overexpression of KLK15 transcripts encoding for both the active isoform and for the isoform 3 in CaP compared to BPH samples. Furthermore, KLK15 transcripts were found to be highly expressed in more aggressive tumors (P = 0.017). These results suggest that KLK15 expression analysis could be employed as a valuable tool for the discrimination between BPH and CaP tissue specimens and as an unfavorable prognostic marker for prostate cancer.