Faculty of Medicine, Laval University, Québec, QC, Canada.
Centre de recherche sur le cancer (CRC) de l'Université Laval, Québec, QC, Canada.
Lipids Health Dis. 2024 Feb 27;23(1):59. doi: 10.1186/s12944-024-02038-8.
Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels.Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC.Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC.
癌细胞的存活和生长需要不断供应脂质。在各种类型的癌症中都观察到了脂质依赖性，包括高级别浆液性卵巢癌（HGSOC），这是一种致命形式的妇科恶性肿瘤。ANGPTL3、PCSK9 和 Apo CIII 是关键的脂质调节因子，并且已经针对每一种开发了治疗性抗体（分别为 Evinacumab、Evolocumab 和 Volanesorsen）。ANGPTL3、PCSK9 和 Apo CIII 在 HGSOC 中的作用（如果有的话）尚不清楚。此外，这些脂质调节因子的水平以前从未在 HGSOC 中报道过。在这项研究中，检查了循环中的 ANGPTL3、PCSK9 和 Apo CIII 水平以及脂质谱，以验证这些脂质调节因子中的一种或多种是否与 HGSOC 相关。
方法 使用 ELISA 试剂盒测量 31 名患有 HGSOC 和 40 名患有良性卵巢病变（BOL）的妇女在治疗和手术前的血浆样本中的 ANGPTL3、PCSK9 和 Apo CIII 水平。罗氏 Modular 分析平台测量了脂质谱、Apo B 和 Lp(a) 水平。
结果 患有 HGSOC 的妇女的 ANGPTL3 水平（84ng/mL，SD：29ng/mL，n=31）高于患有 BOL 的妇女（67ng/mL，SD：31ng/mL，n=40；HGSOC 与 BOL 相比 P=0.019）。BOL 妇女存在脂质谱与 ANGPTL3 之间的关联，以及 HDL-胆固醇与甘油三酯之间的反比关系，但 HGSOC 妇女则没有。PCSK9 和 Apo CIII 与 HGSOC 无关。
结论 在这 71 名妇女的队列中，HGSOC 患者的 ANGPTL3 水平升高。HGSOC 的存在破坏了 HDL 与甘油三酯之间的经典反比关系，以及脂质谱与 ANGPTL3 之间的关联。这些关联仅在无癌症的妇女中维持。鉴于有针对 ANGPTL3 的治疗性抗体 Evinacumab 可用，目前的发现促使人们评估 ANGPTL3 抑制是否在 HGSOC 中具有治疗潜力。
