KLK15 AS A NEW PROGNOSTIC BIOMARKER IN PROSTATE CANCER
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5495Keywords:
Prostate Cancer, KLK15, Kallikrein Related Peptidases, Biomarkers, Gene Expression, Prognosis, Molecular DiagnosticsAbstract
Prostate cancer is one of the most frequently diagnosed malignancies among men worldwide and remains a major public health challenge. Despite significant advances in diagnostic methods, commonly used biomarkers such as prostate-specific antigen (PSA) have important limitations, including relatively low specificity and the risk of overdiagnosis. Consequently, considerable research efforts have focused on identifying novel molecular biomarkers that could improve diagnostic accuracy and provide additional prognostic information in patients with prostate cancer.
Among potential candidates, members of the human tissue kallikrein family (KLKs) have attracted particular attention. These serine proteases are involved in various biological processes, including extracellular matrix remodeling, regulation of the tumor microenvironment, and modulation of cellular signaling pathways. Dysregulation of kallikrein expression has been reported in multiple types of cancer, including prostate cancer.
Kallikrein-related peptidase 15 (KLK15) is one of the members of this family that has recently been investigated in the context of prostate cancer biology. Molecular studies have demonstrated increased KLK15 expression in prostate cancer tissues compared with normal prostate tissue. Furthermore, several studies have indicated associations between KLK15 expression levels and clinicopathological parameters, including tumor stage, Gleason score, and progression of free survival. These findings suggest that KLK15 may represent a promising prognostic biomarker in prostate cancer.
This review summarizes current knowledge regarding the structure and biological function of KLK15, its expression patterns in prostate cancer, and its potential prognostic significance. Although available data indicate that KLK15 may have clinical relevance as a molecular biomarker, further studies involving larger patient cohorts are required to fully establish its diagnostic and prognostic value.
References
Sekhoacha, M., Riet, K., Motloung, P., Gumenku, L., Adegoke, A., & Mashele, S. (2022). Prostate cancer review: Genetics, diagnosis, treatment options, and alternative approaches. Molecules (Basel, Switzerland), 27(17), 5730. https://doi.org/10.3390/molecules27175730
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660
Ahmed, H. U., El-Shater Bosaily, A., Brown, L. C., Gabe, R., Kaplan, R., Parmar, M. K., Collaco-Moraes, Y., Ward, K., Hindley, R. G., Freeman, A., Kirkham, A. P., Oldroyd, R., Parker, C., Emberton, M., & PROMIS Study Group (2017). Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet (London, England), 389(10071), 815–822. https://doi.org/10.1016/S0140-6736(16)32401-1
Loeb, S., Bjurlin, M. A., Nicholson, J., Tammela, T. L., Penson, D. F., Carter, H. B., Carroll, P., & Etzioni, R. (2014). Overdiagnosis and overtreatment of prostate cancer. European Urology, 65(6), 1046–1055. https://doi.org/10.1016/j.eururo.2013.12.062
Thompson, I. M., Pauler, D. K., Goodman, P. J., Tangen, C. M., Lucia, M. S., Parnes, H. L., Minasian, L. M., Ford, L. G., Lippman, S. M., Crawford, E. D., Crowley, J. J., & Coltman, C. A., Jr. (2004). Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. The New England Journal of Medicine, 350(22), 2239–2246. https://doi.org/10.1056/NEJMoa031918
Diamandis, E. P., & Yousef, G. M. (2002). Human tissue kallikreins: A family of new cancer biomarkers. Clinical Chemistry, 48(8), 1198–1205.
Yousef, G. M., Scorilas, A., Jung, K., Ashworth, L. K., & Diamandis, E. P. (2001). Molecular cloning of the human kallikrein 15 gene (KLK15). Up-regulation in prostate cancer. The Journal of Biological Chemistry, 276(1), 53–61. https://doi.org/10.1074/jbc.M005432200
Mavridis, K., Avgeris, M., Koutalellis, G., Stravodimos, K., & Scorilas, A. (2010). Expression analysis and study of the KLK15 mRNA splice variants in prostate cancer and benign prostatic hyperplasia. Cancer Science, 101(3), 693–699. https://doi.org/10.1111/j.1349-7006.2009.01450.x
Adamopoulos, P. G., Koukouzeli, F. Ε., Kontos, C. K., & Scorilas, A. (2020). Identification of six novel alternative transcripts of the human kallikrein-related peptidase 15 (KLK15), using 3'RACE and high-throughput sequencing. Gene, 749, 144708. https://doi.org/10.1016/j.gene.2020.144708
Rabien, A., Fritzsche, F. R., Jung, M., Tölle, A., Diamandis, E. P., Miller, K., Jung, K., Kristiansen, G., & Stephan, C. (2010). KLK15 is a prognostic marker for progression-free survival in patients with radical prostatectomy. International Journal of Cancer, 127(10), 2386–2394. https://doi.org/10.1002/ijc.25435
Yousef, G. M., & Diamandis, E. P. (2001). The new human tissue kallikrein gene family: Structure, function, and association to disease. Endocrine Reviews, 22(2), 184–204. https://doi.org/10.1210/edrv.22.2.0424
Mavridis, K., Stravodimos, K., & Scorilas, A. (2013). Quantified KLK15 gene expression levels discriminate prostate cancer from benign tumors and constitute a novel independent predictor of disease progression. The Prostate, 73(11), 1191–1201. https://doi.org/10.1002/pros.22667
Väänänen, R. M., Lilja, H., Cronin, A., Kauko, L., Rissanen, M., Kauko, O., Kekki, H., Vidbäck, S., Nurmi, M., Alanen, K., & Pettersson, K. (2013). Association of transcript levels of 10 established or candidate-biomarker gene targets with cancerous versus non-cancerous prostate tissue from radical prostatectomy specimens. Clinical Biochemistry, 46(7-8), 670–674. https://doi.org/10.1016/j.clinbiochem.2013.01.019
Michael, I. P., Kurlender, L., Memari, N., Yousef, G. M., Du, D., Grass, L., Stephan, C., Jung, K., & Diamandis, E. P. (2005). Intron retention: A common splicing event within the human kallikrein gene family. Clinical Chemistry, 51(3), 506–515. https://doi.org/10.1373/clinchem.2004.042341
Obiezu, C. V., & Diamandis, E. P. (2005). Human tissue kallikrein gene family: Applications in cancer. Cancer Letters, 224(1), 1–22. https://doi.org/10.1016/j.canlet.2004.09.024
Scorilas, A., & Mavridis, K. (2014). Predictions for the future of kallikrein-related peptidases in molecular diagnostics. Expert Review of Molecular Diagnostics, 14(6), 713–722. https://doi.org/10.1586/14737159.2014.928207
Lawrence, M. G., Lai, J., & Clements, J. A. (2010). Kallikreins on steroids: Structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus. Endocrine Reviews, 31(4), 407–446. https://doi.org/10.1210/er.2009-0034
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Antoni Majda, Natalia Sitko, Paulina Makowska , Joanna Gontarczyk, Alicja Laske , Martyna Sowa , Julia Pająk , Kacper Kucharski , Anna Kamosińska , Adam Kowal, Julia Sokołowska , Marcel Dawidowicz, Hanna Aleksandrowicz
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
