PGK1 expression varies across breast cancer molecular subtypes and is associated with overall survival in the TCGA BRCA cohort

Abstract Purpose Phosphoglycerate kinase 1 (PGK1) is a glycolytic enzyme implicated in cancer metabolism and breast cancer progression, but reported survival associations may be confounded by molecular subtype and stage. Methods We analyzed official TCGA-BRCA PanCancer Atlas RNA-seq V2 RSEM and clinical files from the cBioPortal DataHub. PGK1 expression was evaluated in 1,082 primary tumors, including 981 with PAM50 annotation. Overall-survival analyses included 915 patients in the four principal PAM50 subtypes with complete age, AJCC stage, survival, and expression data (118 deaths). PGK1 was modeled as a standardized continuous variable. The primary Cox model adjusted for age and stratified the baseline hazard by stage and PAM50 subtype. Co-expression was assessed in a curated 119-gene panel using prespecified mean z-score composite signatures. Results PGK1 expression differed across PAM50 subtypes (P = 4.35×10⁻⁵⁷) and was highest in HER2-enriched tumors. Higher PGK1 was associated with shorter overall survival in univariate analysis (hazard ratio [HR] per 1-SD increase, 1.55; 95% CI, 1.31–1.85; P = 7.10×10⁻⁷) and in the primary stratified model (HR, 1.41; 95% CI, 1.13–1.76; P = 0.002). PGK1 correlated most strongly with the glycolysis composite score (r = 0.675; PAM50-adjusted partial r = 0.575). Conclusions PGK1 varies substantially by breast cancer subtype and remains associated with overall survival after accounting for age, stage, and PAM50 subtype. These exploratory single-cohort findings require independent clinical and experimental validation.