Background / synopsis: Cholesterol and lipids play an important role in sustaining tumor growth and metastasis in a large variety of cancers. ANGPTL3 and PCSK9 modify circulating cholesterol levels, thus availability of lipids to peripheral cells. Little is known on the role, if any, of circulating lipid-related factors such as PCSK9, ANGPTL3 and lipoprotein (a) in cancers. Objective/purpose: To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. Methods: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n = 9) or benign (n = 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. Results: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 ± 27.1 ng/mL vs. 78.5 ± 19.3 ng/mL, p < 0.05, n = 14). Moreover, PCSK9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho = 0.34, p < 0.05, n = 46). In contrast, ANGPTL3 and Lp(a) plasma levels did not display any association with breast disease status and lipids did not correlate with disease severity. Conclusion: In this small cohort of 46 women, PCSK9 levels tended to increase with the severity of the breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia, and a potential role in tumor evasion, present results warrant further investigation into a possible association between PCSK9 levels and breast cancer severity in larger cohorts of women.

Over the last decade, computed tomography scanners have gained resolution and have become the standard of care in the investigation of neurologically intact patients suffering from acute headache. The added value of the combined assessment of red blood cells count, visual and spectrophotometric xanthochromia, to detect ruptured aneurysmal subarachnoid hemorrhage (ASAH) following a negative head computed tomography (NHCT) was studied. The population consisted of all patients who had cerebrospinal fluid tested for spectrophotometric xanthochromia between 2003 and 2009 identified through the clinical-laboratory database and who met all the inclusion criteria: >14 years old, had an initial Glasgow Coma Score of 15, a non-traumatic acute headache with a suspected subarachnoid hemorrhage recorded in the initial ED differential diagnosis and an initial negative head CT scan. A total of 706 patients were included. LP identified 5 ASAH (prevalence: 0.7%). In these patients, LP parameters were as follows: high red blood cell count (from 1310 to 63,000×10(6)/L), positive visual xanthochromia in 4 out of 5 ASAH, and positive spectrophotometric xanthochromia in 5 out of 5 ASAH. All ASAH patients were neurologically intact after intervention. No deaths or missed ASAH were reported. Angiographies were performed on 127 patients (19.5%) of which 47 (34.1%) had positive xanthochromia (visual or spectrophotometric). Considering the low prevalence of ASAH following an NHCT, intense resources were utilized to identify all 5 ASAH. Lumbar puncture analyses combining red blood cell count, visual and spectrophotometric xanthochromia identified all ASAH, allowing intervention and a positive clinical outcome. Our data support 1) that LP identifies the presence of a ruptured ASAH after an NHCT and 2)` that a guide to define a subpopulation of patients who would benefit from a lumbar puncture after an NHCT would be desirable.

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer.

Background: 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.Methods: 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.Results: 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.Conclusions: 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.

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.