Multi-dimensional study of Lactate Dehydrogenase A (LDHA) as a Prognostic Indicator and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive cancer type, showing a rising incidence worldwide. Lactate dehydrogenase A (LDHA), which is an essential enzyme involved in glycolysis, plays a significant role in the development of HNSCC, yet its clinical significance and therapeutic potential remain unclear. Methods: We analyzed LDHA expression in HNSCC using multiple omics data, assessing diagnostic potential via ROC analysis and prognostic value through survival analysis. We explored LDHA-related biological pathways using GSEA and GO/KEGG analyses and investigated its impact on immune infiltration and associations with checkpoints. Findings: There was a notable increase in LDHA expression in HNSCC, which was linked to a worse prognosis. Elevated levels of LDHA were associated with the infiltration of immune cells., particularly cytotoxic T lymphocytes, and was positively associated with PD-L1. In vitro, LDHA knockdown reduced HNSCC cell proliferation and invasion. Conclusion: LDHA serves as a promising prognostic biomarker and a therapeutic target in HNSCC, highlighting its significance for immunotherapy. Additional studies are required to confirm these results and to investigate the function of LDHA in the biology of HNSCC.