Abstract
Triple-negative breast cancer (TNBC) is recognized for its aggressive nature, lack of effective diagnosis and treatment, and generally poor prognosis. The objective of this study was to investigate the metabolic changes in TNBC using metabolomics approaches and to explore underlying mechanisms through integrated analysis with transcriptomics. In this study, serum untargeted metabolic profiles were firstly explored between 18 TNBC and 21 healthy controls (HC) by liquid chromatography-mass spectrometry (LC-MS), identifying a total of 22 significantly altered metabolites (DMs). Subsequently, the receiver operating characteristic analysis revealed that 7-methylguanine could serve as a potential biomarker for TNBC in both the discovery and validation sets. Additionally, transcriptomic datasets were retrieved from the GEO database to identify differentially expressed genes (DEGs) between TNBC and normal tissues. An integrative analysis of the DMs and DEGs was subsequently conducted, uncovering potential molecular mechanisms underlying TNBC. Notably, three pathways—tyrosine metabolism, phenylalanine metabolism, and glycolysis/gluconeogenesis—were enriched, explaining the energy metabolism disorders in TNBC. Within these pathways, two DMs (4-hydroxyphenylacetaldehyde and oxaloacetic acid) and six DEGs (MAOA, ADH1B, ADH1C, AOC3, TAT, and PCK1) were identified as critical components. In summary, this study highlights metabolic biomarkers that could potentially be utilized for the diagnosis and screening of TNBC. The comprehensive analysis of metabolomics and transcriptomics data provides a validated and in-depth understanding of TNBC metabolism.