Metastatic prostate cancer was associated with higher levels of triglycerides (2.3 vs 1.7 mmol/L; p=0.0004), Apo CIII, ANGPTL3, and leptin compared to controls.
Case-Control (n=105)
Are levels of PCSK9, ANGPTL3, Apo CIII, leptin, and lipids elevated in metastatic prostate cancer compared to localized prostate cancer and controls?
Whole-body lipid metabolic rewiring, characterized by elevated triglycerides, Apo CIII, ANGPTL3, and leptin, is a feature restricted to the metastatic phase of prostate cancer.
Background/Objectives: 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). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: 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. Conclusions: 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.
Boulay et al. (Tue,) conducted a case-control in Prostate cancer (n=105). Metastatic prostate cancer vs. Localized prostate cancer and controls was evaluated on Levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile. Metastatic prostate cancer was associated with higher levels of triglycerides (2.3 vs 1.7 mmol/L; p=0.0004), Apo CIII, ANGPTL3, and leptin compared to controls.