Metabolic fingerprinting in breast cancer stages through 1H NMR spectroscopy-based metabolomic analysis of plasma

Abstract

Breast cancer (BC) is one of the most common malignancies among women worldwide, which is indeed associated with metabolic reprogramming. However, BC is a very complex and heterogeneous disease, which can relate with the changes in metabolic profiles during BC progression. Hence, investigating the metabolic alterations during BC stage progression may reveal the deregulated pathways and useful metabolic signatures of BC. To demonstrate the metabolic insights, we opted ¹H NMR spectroscopy based metabolomics of blood plasma of early and late stage BC (N = 72) with age and gender matched healthy subjects (N = 50). Further, the metabolic profiles were analyzed to delineate the potential signatures of BC by performing multivariate and nonparametric statistical analysis in early and late stages of BC in comparison with healthy subjects. Sixteen metabolites levels were differentially changed (p < 0.05) in the early and late stages of BC from healthy subjects. Among them, the levels of hydroxybutyrate, lysine, glutamate, glucose, N-acetyl glycoprotein, Lactate were highly distinguished in BC stages and showed a good biomarker potential using receiver-operating curves based diagnostic models. Furthermore, the significant modulation and good diagnostic performances of glutamate, N-acetyl glycoprotein and Lactate in LBC as compared to EBC give their significance in the BC progression. In general, our observations demonstrate that these panels of metabolites may act as vital component of the metabolism of early to late stage BC progression. Our results also open new avenue towards early and late stage BC diagnosis and intervention implying metabolomics approaches.

Keywords: (1)H NMR spectroscopy; Breast cancer; Glutamate; Lactate; Metabolomics; N-acetyl glycoprotein.