Succinylation related gene signature enables risk stratification and prognostic modeling in breast cancer patients

Breast cancer (BRCA) is a major health threat to women and often carries a poor prognosis. Succinylation is closely associated with cancer metabolism; however, research on succinylation-related genes (SRGs) in BRCA remains relatively limited. This study first identified differentially expressed genes between normal and BRCA groups in the TCGA cohort and intersected them with known SRGs to obtain differentially expressed SRGs (DE-SRGs). Univariate Cox and LASSO Cox regression analyses were used to screen the DE-SRGs, followed by multivariate Cox regression to develop a succinylation-related prognostic model. Subsequently, patients were categorized into high and low succinylation-related risk score (SRS) groups according to the median score. Two groups were then compared for differences in immune microenvironment characteristics, somatic mutation burden, and drug sensitivity. Additionally, the expression levels of the signature genes were validated via qRT-PCR. This study developed a prognostic risk model for BRCA patients based on 13 SRGs (ACOT4, ALDH3A1, B3GALT1, IFNG, MMP1, NFKB2, PCSK6, PTK2, SERPINA1, SHMT2, SIRT7, ST3GAL1, and SUCLA2). A markedly elevated infiltration of immune cells was observed in the low-SRS group, including B cells, Mast cells, and Macrophages. The tumor mutational burden was notably lower in the low-SRS group. Drug sensitivity analysis suggested that the high-SRS BRCA patients might be more susceptible to FTI-277 and GNF-2. qRT‑PCR results showed that ACOT4, IFNG, MMP1, NFKB2, PCSK6, PTK2, SHMT2, SIRT7, and ST3GAL1 were significantly upregulated in human BRCA cell lines, while ALDH3A1, B3GALT1, and SUCLA2 were significantly downregulated. Our findings highlight the prognostic value of SRGs in BRCA, laying the groundwork for its potential use in guiding personalized treatment.