Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls).
Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform.
The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort.
In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa.
Cancers. 2026 Apr 07*** epublish ***
Gabriel Boulay, Marwan Khodr, Ann-Charlotte Bergeron, Émilie Wong Chong, France-Hélène Joncas, Chloé Castonguay, Karine Robitaille, Hélène Hovington, Vincent Fradet, Alain Bergeron, Frédéric Pouliot, Jonatan Blais, Nabil G Seidah, Frédéric Calon, Anne Gangloff
Faculté de Pharmacie, Université Laval, Québec City, QC G1V 0A6, Canada., Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada., Axe Oncologie, Centre de Recherche du CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada., Unité de Recherche en Biochimie Neuroendocrinienne, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.