Two effective models based on comprehensive lipidomics and metabolomics can distinguish BC versus HCs, and TNBC versus non-TNBC

Background: Lipidomics and metabolomics are closely related to tumor phenotypes, and serum lipoprotein subclasses and small-molecule metabolites are considered as promising biomarkers for breast cancer (BC) diagnosis. This study aimed to explore potential biomarker models based on lipidomic and metabolomic analysis that could distinguish BC from healthy controls (HCs) and triple-negative BC (TNBC) from non-TNBC.

Methods: Blood samples were collected from 114 patients with BC and 75 HCs. A total of 112 types of lipoprotein subclasses and 30 types of small-molecule metabolites in the serum were detected by ¹ H-NMR. All lipoprotein subclasses and small-molecule metabolites were subjected to a three-step screening process in the order of significance (p < 0.05), univariate regression (p < 0.1), and lasso regression (nonzero coefficient). Discriminant models of BC versus HCs and TNBC versus non-TNBC were established using binary logistic regression.

Results: We developed a valid discriminant model based on three-biomarker panel (formic acid, TPA2, and L6TG) that could distinguish patients with BC from HCs. The area under the receiver operating characteristic curve (AUC) was 0.999 (95% confidence interval [CI]: 0.995-1.000) and 0.990 (95% CI: 0.959-1.000) in the training and validation sets, respectively. Based on the panel (D-dimer, CA15-3, CEA, L5CH, glutamine, and ornithine), a discriminant model was established to differentiate between TNBC and non-TNBC, with AUC of 0.892 (95% CI: 0.778-0.967) and 0.905 (95% CI: 0.754-0.987) in the training and validation sets, respectively.

Conclusion: This study revealed lipidomic and metabolomic differences between BC versus HCs and TNBC versus non-TNBC. Two validated discriminatory models established against lipidomic and metabolomic differences can accurately distinguish BC from HCs and TNBC from non-TNBC.

Impact: Two validated discriminatory models can be used for early BC screening and help BC patients avoid time-consuming, expensive, and dangerous BC screening.