Corrigendum to “Simultaneous quantification and natural 13C abundance of fatty acids in breast cancer tissues and serum by GC-C-IRMS for tumor characterization”

Breast cancer (BrCa) is a heterogeneous disease which complicates early detection, subtyping, and treatment selection. Metabolic alterations are hallmarks of cancer, but current methods to study metabolism, especially stable isotope analysis, involve complex workflows, derivatization steps, and have limited clinical use. Lipid metabolism is altered in BrCa, yet sensitive and minimally invasive tools to quantify fatty acid (FA) isotope signatures are lacking. Here, we present a novel gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) method for direct δ 13 C (carbon isotope composition) and concentration analysis of underivatized FAs in tissues and serum, with excellent repeatability, reproducibility, and minimal matrix effects. The optimized method involves simple lipid hydrolysis without derivatization, followed by FA separation on a polar GC column, and is validated for both quantification and isotopic analysis using internal standards. Application to human tissue and serum samples from patients with different BrCa subtypes revealed significant natural 13 C enrichment in C16:0, C16:1, and C18:1, alongside a decrease in C14:0 and C16:1 concentrations in cancerous compared to adjacent non-cancerous tissue, reflecting FA metabolic reprogramming during carcinogenesis. Importantly, δ¹³C values of C18:0 and C18:2 differed between BrCa subtypes in both cancerous tissue and serum. This study presents the first GC-C-IRMS method enabling high-precision, direct analysis of underivatized FAs in tissues and serum with minimal sample preparation. The approach provides a promising minimally invasive tool for characterizing FA metabolism and for improving breast cancer detection, subtyping, and metabolic phenotyping without isotopic labeling.