Bergeron Ann-Charlotte, Wong-Chong Emilie, Joncas France-Hélène, Castonguay Chloé, Calon Frédéric, Seidah Nabil G, Blais Jonatan, Robitaille Karine, Bergeron Alain, Fradet Vincent, Gangloff Anne
Oncology Research Axis, Centre de Recherche du CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
Division of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada.
Cancer Med. 2025 Feb;14(3):e70587. doi: 10.1002/cam4.70587.
Some cancers have been found to require abundant supplies of lipids for their development. One example is prostate cancer (PCa). To date, lipid-modifying factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like 3 protein (ANGPTL3), and lipoprotein(a) or Lp(a), have not been reported in men with PCa. The present study aimed to verify whether plasma levels of these lipid-related proteins vary in men with PCa compared to at-risk but cancer-free men.
Plasma samples from 35 men with locally advanced PCa Gleason 8 and 9 versus 35 men at risk of PCa were selected as cases and controls. Blood samples were paired according to age and BMI. Apolipoprotein B100 (Apo B), Lp(a), and lipid profiles were measured on an analytical platform (Roche Cobas). PCSK9 and ANGPTL3 levels were determined by ELISA.
No significant change in lipids and related factors levels was observed between men with localized PCa Gleason 8 or 9 and matched controls. A correlation between ANGPTL3 and HDL levels was only confirmed in controls (ρ = 0.54, p = 0.0009). PCSK9 was inversely associated with PSA levels in the entire cohort (ρ = -0.31, p < 0.01), suggesting that factors influencing PCSK9 could also influence PSA levels. In controls only, PSA levels were correlated with LDL, Apo B, non-HDL, total cholesterol, and triglycerides (all ρ coefficients ≥ 0.35, all p-values < 0.05). PCSK9 was correlated to LDL in PCa men, but the relationship was unexpectedly found to be inverse.
In this observational study, lipid profiles, PCSK9, ANGPTL3, and Lp(a) levels did not change in men diagnosed with locally advanced Gleason 8 or 9 PCa compared to at-risk but cancer-free men. The present data suggest a complex interplay between PCSK9, PSA, and the lipid profile in localized PCa.
已发现某些癌症在发展过程中需要大量脂质供应。前列腺癌（PCa）就是一个例子。迄今为止，尚未在前列腺癌男性患者中报道脂质修饰因子，如前蛋白转化酶枯草溶菌素/克新9型（PCSK9）、血管生成素样3蛋白（ANGPTL3）和脂蛋白（a）或Lp（a）。本研究旨在验证与有前列腺癌风险但无癌症的男性相比，这些脂质相关蛋白的血浆水平在前列腺癌男性患者中是否存在差异。
选取35例局部晚期Gleason 8和9级前列腺癌男性患者与35例有前列腺癌风险的男性患者的血浆样本作为病例组和对照组。根据年龄和体重指数对血样进行配对。在分析平台（罗氏Cobas）上测量载脂蛋白B100（Apo B）、Lp（a）和血脂谱。通过酶联免疫吸附测定法（ELISA）测定PCSK9和ANGPTL3水平。
在局限性Gleason 8或9级前列腺癌男性患者与匹配的对照组之间，未观察到脂质及相关因子水平有显著变化。仅在对照组中证实ANGPTL3与高密度脂蛋白（HDL）水平之间存在相关性（ρ = 0.54，p = 0.0009）。在整个队列中，PCSK9与前列腺特异性抗原（PSA）水平呈负相关（ρ = -0.31，p < 0.01），这表明影响PCSK9的因素也可能影响PSA水平。仅在对照组中，PSA水平与低密度脂蛋白（LDL）、Apo B、非HDL、总胆固醇和甘油三酯相关（所有ρ系数≥ 0.35，所有p值< 0.05）。在前列腺癌男性患者中，PCSK9与LDL相关，但出乎意料地发现这种关系是相反的。
在这项观察性研究中，与有前列腺癌风险但无癌症的男性相比，被诊断为局部晚期Gleason 8或9级前列腺癌的男性患者的血脂谱、PCSK9、ANGPTL3和Lp（a）水平没有变化。目前的数据表明在局限性前列腺癌中PCSK9、PSA和血脂谱之间存在复杂的相互作用。
