ANGPTL3, Apo CIII, Leptin and Triglycerides Are Elevated in Metastatic Prostate Cancer

Figures

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  Figure 1. Roles of ANGPTL3, Apo CIII, and leptin in delivering triglycerides to tissues and cancer cells. Similarly to regular cells, cancer cells can obtain lipids from triglyceride-rich lipoproteins (TRLs) originating from dietary lipid uptake transferred into chylomicrons or through very-low-density lipoproteins (VLDLs) originating from the liver. (a) Triglycerides are delivered to peripheral tissues (adipose, muscles, and heart) through TRLs for energy use and storage. This process is regulated by the breakdown of triglycerides into fatty acids using lipoprotein lipase (LPL). Apo CII found on lipoproteins activates LPL, allowing the hydrolysis of triglycerides into free fatty acids and their subsequent uptake by tissues. Large TRLs can be transformed into intermediate-density lipoproteins (IDLs), low-density lipoproteins (LDLs), and TRL remnants as their size diminishes. LDL particles interact with LDL receptors (LDLR) present on the surface of the liver and peripheral tissues, where they can be internalized and processed in endosomes, leading to the removal of cholesterol from the blood. (b) ANGPTL3 is primarily produced by the liver and can have far-reaching effects, inhibiting…

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  Figure 2. Box plots showing circulating levels of ANGPTL3 (a), Apo CIII (b), leptin (c), PCSK9 (d), Lp(a) (e), and triglycerides (f) between men at risk of PCa (controls), men with localized high-grade PCa and men with metastatic PCa (n = 35/group). The centre line represents the median, the box spans the 1st and 3rd quartiles, and the whiskers indicate the smallest or largest values. A two-sided ANCOVA using age and BMI as covariates was performed on log-transformed data of variables that showed a Gaussian distribution, and a two-sided generalized linear model (GLM) using the Tweedie distribution with age and BMI as covariates was applied to variables with non-Gaussian distributions. *: p < 0.05, **: p < 0.01, ***: p < 0.001.

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  Figure 3. Matrices of pairwise Spearman’s correlation analyses between all study variables. Pairwise correlations are shown for patients at risk of PCa ((a), n = 35), patients diagnosed with localized high-grade PCa ((b), n = 35), patients diagnosed with metastatic PCa ((c), n = 35), and the entire cohort ((d), n = 105). Correlation coefficients (rho) are displayed with colour hues indicative of relationship strength (red: positive correlation, blue: negative correlation). Significant values are indicated in boldface (two-sided p-values: *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001).

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  Figure 4. PCSK9 levels as a function of circulating LDL. A linear regression shows an inverse correlation between PCSK9 and LDL levels in men at risk of prostate cancer (PCa), men with localized PCa and men with metastatic PCa (n = 35/group). This finding is unexpected as PCSK9 elevates cholesterol by destroying hepatic LDL-R. The slope of the linear regression is shown on the graph.