Circulating levels of PCSK9, ANGPTL3 and Lp(a) in stage III breast cancers

Abstract

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.

Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer—Evidence from a 17-Year Follow-Up Study

“…Indeed, only one recent study on a small sample size (n = 46) of women with stage III breast cancer has been conducted, reporting increasing levels of PCSK9 with the severity of breast disease. However, no prognostic conclusions were made [14]. A pancancer analysis found that PCSK9 expression was considerably higher in invasive breast We also evaluated the influence of other risk biomarkers, both as confounders and risk stratifiers, and different cut-off points for PCSK9, but the results did not change.…”

“…Indeed, only one recent study on a small sample size (n = 46) of women with stage III breast cancer has been conducted, reporting increasing levels of PCSK9 with the severity of breast disease. However, no prognostic conclusions were made [14]. A pan-cancer analysis found that PCSK9 expression was considerably higher in invasive breast carcinoma [24].…”

“…With the scope of exploring its role as a biomarker element, circulating plasma PCSK9 levels were evaluated in 14 women with a benign breast condition, in 9 with stage 0, and in 23 with a stage III breast tumor. The latter group exhibited significantly increased levels compared to age-matched counterparts with a benign lesion [14]. Genetic studies have demonstrated that LDL-cholesterol-lowering variants in PCSK9, responsible for reduced levels of LDL, were associated with either a risk-reducing [15] or a neutral effect on breast cancer [16].…”

Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside

“… 331 This observation is in harmony with a recent clinical study involving 46 cases, which suggested that PCSK9 levels could escalate in proportion to the severity of breast disease, with the lowest levels found in benign disorders while the highest in stage III breast cancer. 333 Such evidence accentuates the potential utility of PCSK9 as a diagnostic and prognostic biomarker in breast cancer.…”

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

“…Patients with liver cirrhosis exhibit lower serum PCSK9 levels, while these levels are increased in patients with hepatitis C virus (HCV)-induced liver cirrhosis ( 52 ). PCSK9 levels increase with the severity of breast cancer ( 53 ). These specific pathological conditions may lead to changes in thrombosis or haemostasis.…”