Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary
Abstract 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-modula...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-024-02038-8 |
| _version_ | 1797273377847640064 |
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| author | Emilie Wong Chong France-Hélène Joncas Pierre Douville Dimcho Bachvarov Caroline Diorio Frédéric Calon Ann-Charlotte Bergeron Jonatan Blais Shuk On Annie Leung Nabil Georges Seidah Anne Gangloff |
| author_facet | Emilie Wong Chong France-Hélène Joncas Pierre Douville Dimcho Bachvarov Caroline Diorio Frédéric Calon Ann-Charlotte Bergeron Jonatan Blais Shuk On Annie Leung Nabil Georges Seidah Anne Gangloff |
| author_sort | Emilie Wong Chong |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:43:30Z |
| format | Article |
| id | doaj.art-3e08325700c543e7b2a228d6e9b32a33 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-03-07T14:43:30Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-3e08325700c543e7b2a228d6e9b32a332024-03-05T20:08:05ZengBMCLipids in Health and Disease1476-511X2024-02-0123111010.1186/s12944-024-02038-8Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovaryEmilie Wong Chong0France-Hélène Joncas1Pierre Douville2Dimcho Bachvarov3Caroline Diorio4Frédéric Calon5Ann-Charlotte Bergeron6Jonatan Blais7Shuk On Annie Leung8Nabil Georges Seidah9Anne Gangloff10Faculty of Medicine, Laval UniversityCentre de recherche sur le cancer (CRC) de l’Université LavalFaculty of Medicine, Laval UniversityFaculty of Medicine, Laval UniversityFaculty of Medicine, Laval UniversityFaculty of Pharmacy, Laval UniversityFaculty of Medicine, Laval UniversityFaculty of Medicine, Laval UniversityRéseau de Recherche sur le CancerLaboratory of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de MontréalFaculty of Medicine, Laval UniversityAbstract 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.https://doi.org/10.1186/s12944-024-02038-8ANGPTL3EvinacumabPCSK9Apo CIIILp(a)Lipid profile |
| spellingShingle | Emilie Wong Chong France-Hélène Joncas Pierre Douville Dimcho Bachvarov Caroline Diorio Frédéric Calon Ann-Charlotte Bergeron Jonatan Blais Shuk On Annie Leung Nabil Georges Seidah Anne Gangloff Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary Lipids in Health and Disease ANGPTL3 Evinacumab PCSK9 Apo CIII Lp(a) Lipid profile |
| title | Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary |
| title_full | Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary |
| title_fullStr | Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary |
| title_full_unstemmed | Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary |
| title_short | Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary |
| title_sort | pre operative levels of angiopoietin protein like 3 angptl3 in women diagnosed with high grade serous carcinoma of the ovary |
| topic | ANGPTL3 Evinacumab PCSK9 Apo CIII Lp(a) Lipid profile |
| url | https://doi.org/10.1186/s12944-024-02038-8 |
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