Plasma ANGPTL3, Apo CIII, leptin, and lipid levels in patients with metastatic prostate cancer.
Bibliographic record
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".