Altered Levels of Desaturation and ω-6 Fatty Acids in Breast Cancer Patients’ Red Blood Cell Membranes

Abstract

Red blood cell (RBC) membrane can reflect fatty acid (FA) contribution from diet and biosynthesis. In cancer, membrane FAs are involved in tumorigenesis and invasiveness, and are indicated as biomarkers to monitor the disease evolution as well as potential targets for therapies and nutritional strategies. The present study provides RBC membrane FA profiles in recently diagnosed breast cancer patients before starting chemotherapy treatment. Patients and controls were recruited, and their dietary habits were collected. FA lipidomic analysis of mature erythrocyte membrane phospholipids in blood samples was performed. Data were adjusted to correct for the effects of diet, body mass index (BMI), and age, revealing that patients showed lower levels of saturated fatty acids (SFA) and higher levels of monounsaturated fatty acid, cis-vaccenic (25%) than controls, with consequent differences in desaturase enzymatic index (∆9 desaturase, –13.1%). In the case of polyunsaturated fatty acids (PUFA), patients had higher values of ω-6 FA (C18:2 (+11.1%); C20:4 (+7.4%)). RBC membrane lipidomic analysis in breast cancer revealed that ω-6 pathways are favored. These results suggest new potential targets for treatments and better nutritional guidelines.

Lipidomic landscape in cancer: Actionable insights for membrane‐based therapy and diagnoses

“…Thus, FA profiling can provide information on the balance of various molecular components in erythrocyte phospholipids. Importantly, findings from this and other groups have substantiated FA‐based membrane lipid profiling as a robust biomarker of lipid metabolic changes in various samples from cancer patients 29,118,119 . PUFAs are mainly sourced from diet and once inside the cell, they are modified to produce more PUFAs, eventually incorporated into cell membranes regulating membrane function.…”

“…In addition, alterations in FA pools also govern the interplay between metabolic, genetic, and dietary changes. Going one step further, the same group revealed that using membranes of mature erythrocytes or red blood cells (RBCs) is the best sampling method to assess FA‐based membrane lipidomic changes 29,119 . Extracting RBC membranes for FA analysis is relatively inexpensive and noninvasive, and RBC membrane composition is representative of all FA families.…”

“…Therefore, evaluating the relationship between dietary or nutritional factors and lipidomic rewiring in various cancers can aid in the development of personalized cancer treatments. Altered lipid profiles in RBC membranes have been found to be independent of dietary habits in patients with various cancer types, suggesting that de novo synthesis of FAs and altered metabolism of ω‐6FA are the predominant altered pathways in cancer 118,119 …”

Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines

“…We believe that knowledge on fatty acid-based membrane lipidome analysis will expand the understanding of lipid metabolism and individuate related biomarkers which are applicable as translational molecular medicine tools. Because lipids are an important part of human nutrition, especially in evaluating unsaturated fatty acid intakes, integrated molecular diagnostic profiles of breast cancer patients can be envisaged as easy-to-use screening for the design of tailored dietary regimes, as is emerging in recent clinical observational studies [ 47 , 48 ].…”

The Effect of Genistein Supplementation on Cholesterol Oxidation Products and Fatty Acid Profiles in Serums of Rats with Breast Cancer

“…Interestingly, this ratio was significantly the lowest in the control group of animals and highest in animals supplemented with micro- and nanogenistein. In two of her publications [ 34 , 35 ], Amézaga presented the results of studies that showed the concentration of saturated fatty acids to be lower in cancer patients than in the healthy control group. Since no cell can exist without membranes, the need to build new membranes is a priority in the process of cell replication.…”