Abstract
Simple SummaryLipids’ metabolism deregulation is an established mark of breast cancer, however, no conclusive results have been reported on its effective role in disease development and progression. In this study, we applied straightforward 1H-NMR analysis to deeply explore alterations in circulating lipoproteins in HER2-positive breast cancer patients. The results support the key role played by lipids in the development of this breast cancer histotype and point out a specific lipid trait, characterized by a high plasma level of VLDL subfractions, potentially useful for diagnostic purposes. Moreover, the monitoring of plasma lipoproteins profile changes along the therapeutic interventions was found valuable to predict the clinical outcome.The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline 1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients’ group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of 1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.
Highlights
Cellular lipid metabolism reprogramming is a well-recognized hallmark of cancer disease [1,2,3] generally characterized by an increased lipogenesis and lipid storage, needful for the rapid tumour growth and metastatic spread [4,5,6,7]
The present study aimed to explore the potential of 1 H-NMR lipoproteins and lipids profile analysis for the discovery of potential novel diagnostic and prognostic biomarkers of HER2-positive breast cancer (BC)
The two groups did not differ for the body mass index (BMI) (p = 0.801) with a prevalence of normal weight (BMI < 25) in both groups corresponding to 64.7% of the BC patients and
Summary
Cellular lipid metabolism reprogramming is a well-recognized hallmark of cancer disease [1,2,3] generally characterized by an increased lipogenesis and lipid storage, needful for the rapid tumour growth and metastatic spread [4,5,6,7]. De novo lipogenesis is a common marker of precursor lesions, cancer cells are able to uptake lipids from the tumour microenvironment [8,9]. In this context, the main extra-tumour source of lipids is represented by triglycerides (TGs) derived from the surrounding adipose tissues and lipoproteins from the bloodstream [8,10]. The main extra-tumour source of lipids is represented by triglycerides (TGs) derived from the surrounding adipose tissues and lipoproteins from the bloodstream [8,10] These latter are supramolecular protein–lipids complex with a hydrophobic core of TGs and esterified cholesterol (Chol), surrounded by a double layer of phospholipids (PLs), free-Chol, and apolipoproteins (Apo) that drive their final structure and function [11]. The VLDLs and LDLs are mainly responsible for the delivery of TGs and Chol to peripheral tissues while HDLs have a scavenger function transporting Chol and lipids from peripheral tissues to the liver [13,14,15,16,17,18]
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