The prevailing biomarker employed for prostate cancer (PCa) screening and diagnosis is the prostate-specific antigen (PSA). Despite excellent sensitivity, PSA lacks specificity, leading to false positives, unnecessary biopsies and overdiagnosis. Consequently, PSA is increasingly less used by clinicians, thus underscoring the imperative for the identification of new biomarkers. An emerging biomarker in this context is citrate, a molecule secreted by the normal prostate, which has been shown to be inversely correlated with PCa. Here, we discuss about PSA and its usage for PCa diagnosis, its lack of specificity, and the various conditions that can affect its levels. We then provide our vision about what we think would be a valuable addition to our PCa diagnosis toolkit, citrate. We describe the unique citrate metabolic program in the prostate and how this profile is reprogrammed during carcinogenesis. Finally, we summarize the evidence that supports the usage of citrate as a biomarker for PCa diagnosis, as it can be measured in various patient samples and be analyzed by several methods. The unique relationship between citrate and PCa, combined with the stability of citrate levels in other prostate-related conditions and the simplicity of its detection, further accentuates its potential as a biomarker.
The Journal of steroid biochemistry and molecular biology. 2024 Jul 16 [Epub ahead of print]
Lucas Galey, Ayokunle Olanrewaju, Hermann Nabi, Jean-Sébastien Paquette, Frédéric Pouliot, Étienne Audet-Walsh
Endocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec City, Canada., Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA; Department of Bioengineering, University of Washington, Seattle, Washington, USA., Centre de recherche sur le cancer de l'Université Laval, Québec City, Canada., Laboratoire de recherche et d'innovation en médecine de première ligne (ARIMED), Groupe de médecine de famille universitaire de Saint-Charles-Borromée, CISSS Lanaudière, Saint-Charles-Borromée, QC, Canada; VITAM Research Centre for Sustainable Health, Québec, QC, Canada; Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada., Centre de recherche sur le cancer de l'Université Laval, Québec City, Canada; Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada; Department of surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada., Endocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec City, Canada. Electronic address: .