1H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients

Abstract

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.

Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment

“…Patients that received chemotherapy had finished treatment at least three weeks before radiation. Chemotherapy has been shown to have a transiently dyslipidemic effect, with changes becoming less apparent over time ( 22 , 46 , 48 ). In line with this, the lipid profile of chemotherapy recipients became more similar to that of non-recipients over the course of treatment.…”

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

“…However, in individuals with HER2-positive BC, the analysis of the lipoprotein profile using nuclear magnetic resonance demonstrated an enhanced level of specific VLDL subfractions, which served as a marker of plasma lipid alteration compared to control women, even with similar BMI between the groups. Reductions in HDL subfractions were surrogate markers for the response to neoadjuvant chemotherapy follow-up 56 .…”

Novel metabolomics-biohumoral biomarkers model for predicting survival of metastatic soft-tissue sarcomas

“… 40 , 41 High levels of LDL and VLDL triglycerides derived from tumor-host interplay were recently observed in human epidermal growth factor receptor 2 (HER2) positive breast cancer, suggesting that mobilization of the triglyceride LDL subfractions may represent a surrogate index of aggressiveness. 42 Analogously, the increase of triglycerides-LDL cargo in plasma of mSTS patients may reflect a unique host tumor-induced metabolic reprogramming aimed at fueling the tumor for its lipid needs. 43 , 44 …”