Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors

Abstract

The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.

The Role of Apolipoproteins in the Commonest Cancers: A Review

“…However, the level of APOB was higher in triple-negative breast cancer patients in comparison to other molecular types [37]. Yet their APOB levels were comparable in all stages of breast cancer [37].…”

“…According to a recent study, the total cholesterol to APOB ratio did not distinguish between breast cancer patients and control patients [37]. However, the level of APOB was higher in triple-negative breast cancer patients in comparison to other molecular types [37]. Yet their APOB levels were comparable in all stages of breast cancer [37].…”

“…However, in this study, APOA1 proved to be a more effective biomarker for distinguishing intra-ocular metastasis compared to APOB. According to a recent study, the total cholesterol to APOB ratio did not distinguish between breast cancer patients and control patients [37]. However, the level of APOB was higher in triple-negative breast cancer patients in comparison to other molecular types [37].…”

Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer

“…In this particular case, the majority of advanced-stage breast cancer cases were of the TN molecular type. Furthermore, TN cases exhibited higher levels of plasma lipids, which facilitated the channeling of metabolites necessary for cell replication [ 24 ]. On the other hand, HDLs in TN breast cancer demonstrated an enhanced ability to delay the oxidation of LDL in vitro compared to HDLs from control subjects, even without alterations in HDL particle composition [ 25 ].…”