Plasma ANGPTL3, Apo CIII, leptin, and lipid levels in patients with metastatic prostate cancer.

Abstract

e17054 Background: Abundant cholesterol supplies are required to sustain tumor growth and metastasis. Metastatic prostate cancers (PCa) are no exception. Since powerful cholesterol-lowering drugs have been developed in recent years to treat cardiovascular disease, verifying whether these drugs can induce a cholesterol shortage sufficient to slow or halt the progression of PCa is intuitive. However, little is known about the levels of hyperlipidemic factors in metastatic PCa, which are now targetable through cholesterol-lowering drugs. Thus, we investigated the hypothesis that metastatic prostate cancer might lead to increased circulating levels of hyperlipidemic factors such as PCSK9, ANGPTL3, and Apo CIII. Methods: Plasma levels of analytes in men diagnosed with metastatic PCa (mPCa) were compared to those with high-grade (Gleason 8 or 9) localized PCa, and men at risk of PCa, as controls (n=35 per group). PCSK9, ANGPTL3, Apo CIII, and leptin were measured using commercial ELISA kits (Biolegends, Abcam, ThermoFisher Scientific). Lp(a), the lipid profile (total cholesterol, triglycerides, HDL-Cholesterol, Apo B), free and total PSA were measured on a Roche Cobas analytical platform, whereas LDL and non-HDL-Cholesterol were calculated. Analyses of covariance (variables with Gaussian distribution) or generalized linear models (non-Gaussian), followed by post-hoc pairwise comparisons, were performed with JMP Pro 17.2 and SAS 9.4 with age and BMI as covariates. Results: As expected, PSA levels were higher in men with PCa, especially in metastatic patients, and the free-to-total PSA ratio was low in all groups (mean = 0.16 ± 0.09). The lipid panel was not different between groups except for triglycerides, which were higher in mPCa. ANGPTL3 and Apo CIII were increased in metastatic patients vs controls and localized PCa. The cancer status did not affect PCSK9 nor Lp(a) levels. Leptin also appeared elevated in the metastatic group. Conclusions: We observed an increase in levels of ANGPTL3, Apo CIII, triglycerides, and leptin in metastatic PCa compared to individuals belonging to the localized PCa Gleason 8 or 9 group or the at-risk individuals. Since the latter two groups had similar ANGPTL3, Apo CIII, leptin, and triglycerides levels, the increase in these factors seems to only happen at the metastatic stage. Given the availability of drugs targeting ANGPTL3 and Apo CIII, these targets need further assessment as potential therapy in metastatic prostate cancer. This study was supported by establishment funds from the CHU de Quebec Foundation and the FRQS. Key results. Mean ± SD Post-hoc testp-value mPCa At Risk Localized PCa mPCa PSA (ng/mL) 5.77 ± 4.75 13.0 ± 12.4 174.0 ± 351.0 < 0.05 Trig. (mmol/L) 1.70 ± 1.19 1.47 ± 0.66 2.32 ± 1.19 < 0.01 ANGPTL3 (ng/mL) 41.7 ± 20.3 42.8 ± 24.4 57.3 ± 27.3 0.0469 (vs CTL) Apo CIII (µg/mL) 110.7 ± 56.5 115.0 ± 58.5 159.9 ± 98.1 < 0.05 Leptin (ng/mL) 9.57 ± 9.23 8.18 ± 7.96 17.7 ± 18.1 < 0.01