LDHA as a predictive biomarker and its association with the infiltration of immune cells in pancreatic adenocarcinoma

Background: Lactate dehydrogenase A ( LDHA ) plays a crucial role in the final step of anaerobic glycolysis, converting L-lactate and NAD+ + to pyruvate and nicotinamide adenine dinucleotide (NADH). Its high expression has been linked to tumorigenesis and patient survival in various human cancers. However, the full implications of LDHA's 's role and its correlation with clinicopathological features in pancreatic adenocarcinoma (PAAD) remain to be fully understood. This study was thus conducted to elucidate the specific functions of LDHA in PAAD, with the aim of providing more robust evidence for clinical diagnosis and treatment. Methods: In an extensive systems analysis, we searched through numerous databases, including The Cancer Genome Atlas (TCGA) and Oncomine. Our objective was to clarify the clinical implications and functional role of LDHA in PAAD. Bioinformatics was used to identify the biological function of LDHA expression and its correlation with tumor immune status. Results: Our analysis revealed that the LDHA gene is overexpressed in PAAD and that this upregulation was associated with a worse patient prognosis. Through gene set enrichment analysis, we found that LDHA's 's influence on PAAD is linked to signaling pathways involving Kirsten rat sarcoma viral oncogene homolog (K K-Ras), ), transforming growth factor-beta ( TGF-beta ), and hypoxia inducible factor-1 ( HIF-1 ). Mutation of K-Ras could upregulate its own expression and was positively correlated with LDHA expression. Moreover, our data demonstrated that LDHA expression was linked to immune infiltration and poor prognosis in PAAD, indicating its role in disease pathogenesis. Overexpression of LDHA may suppress tumor immunity, suggesting it as a potential target for the diagnosis and treatment of PAAD, thus providing new insights into managing this aggressive cancer. Conclusions: Overall, our results showed that LDHA as a prognostic biomarker could serve as a novel target for future PAAD immunotherapy.