Expression of glycolytic enzymes (GLUT1, HK2, PKM2, LDH-A) and their association with tumour stage and clinicopathological characteristics in breast cancer patients

Abstract

Objective: Cancer cells reprogramme their metabolism toward aerobic glycolysis (Warburg effect), a process driven by key enzymes and transporters. This study evaluated serum levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDH-A) in breast cancer patients before and after chemotherapy, and assessed their diagnostic performance.

Methods: A case–control study enrolled 120 women (30 untreated breast cancer, 30 post‑chemotherapy, and 60 age‑matched healthy controls) in Thi‑Qar, Iraq. Serum biomarkers were quantified using enzyme‑linked immunosorbent assays. Fasting blood glucose and lactate were measured enzymatically. Statistical analyses included ANOVA with Tukey’s post hoc test, Pearson correlation, receiver operating characteristic (ROC) curves, and Cohen’s d effect size. In silico validation used TCGA and GEO datasets.

Results: Pre‑treatment patients showed significantly elevated lactate, FBS, LDH‑A, GLUT1, and PKM2 compared with post‑treatment and control groups (p < 0.001). Post‑chemotherapy levels decreased but remained above controls for most markers except HK2, which was unexpectedly higher in controls. PKM2 and LDH‑A demonstrated excellent diagnostic accuracy (AUCs of 0.98 and 0.97, respectively). Correlation analysis revealed a positive association between PKM2 and FBS (r = 0.572, p = 0.001). Effect sizes were large for LDH‑A and PKM2.

Conclusion: Serum PKM2 and LDH‑A are promising non‑invasive diagnostic biomarkers for breast cancer and may help monitor treatment response, despite the unexpected behaviour of HK2, which warrants further investigation.