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INTERNATIONAL CONGRESS OF

CancerGenetics

• Lactate Dehydrogenase A Overexpression and Tumor Microenvironment Acidosis in Triple-Negative Breast Cancer: A Systematic Review

• Alireza Pourrahim,^1,* Mohammad Mahdi Pourrahim,² Omid Raiesi,³ Alireza Vasiee,⁴
  1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
  2. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
  3. Omid Raiesi
  4. Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran
  
  
  
• Introduction: Triple-negative breast cancer (TNBC) relies heavily on glycolytic flux, driven by lactate dehydrogenase A (LDH-A), to sustain rapid proliferation. LDH-A–mediated conversion of pyruvate to lactate contributes to extracellular acidification, which in turn promotes invasion, chemoresistance, and poor survival. We systematically reviewed the literature to quantify the relationship between LDH-A overexpression, extracellular pH, and clinical outcomes in TNBC.
• Methods: We searched PubMed, EMBASE, Web of Science, and Cochrane Library up to June 2025 for studies assessing LDH-A protein or mRNA levels and tumor pH metrics in TNBC patients. Search terms included (“LDHA” OR “lactate dehydrogenase A”) AND (“acidosis” OR “pH”) AND (“triple-negative breast cancer”). Two reviewers independently screened 1,243 records, extracted continuous and survival data, and evaluated study quality using the Newcastle–Ottawa Scale.
• Results: Eight studies (n = 1,124 TNBC patients; median follow-up 48 months) met inclusion criteria. Pooled LDH-A expression was significantly higher in TNBC versus non-TNBC controls (SMD 1.12; 95% CI 0.85–1.39; p < 0.01). Extracellular tumor pH in high-LDH-A cohorts was lower by an SMD of −0.75 (95% CI −0.95 to −0.55; p < 0.001). High LDH-A expression was associated with poorer OS (pooled HR 2.03; 95% CI 1.65–2.50; p < 0.01) and DFS (HR 1.87; 95% CI 1.50–2.34; p < 0.001). Subgroup analyses showed consistent effects regardless of detection modality (IHC vs. qPCR) and geographic region.
• Conclusion: LDH-A overexpression in TNBC correlates with a significantly more acidic tumor microenvironment and predicts a twofold increase in mortality and recurrence risk. These findings support LDH-A as both a prognostic biomarker and a therapeutic target to modulate tumor acidosis and improve clinical outcomes.
• Keywords: lactate dehydrogenase A; tumor acidosis; breast cancer; extracellular pH