Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer

Background: Pancreatic cancer (PC) has the lowest 5-year survival rate; therefore, new early screening methods and therapeutic targets are still urgently required. Emerging technologies such as metabolomicbased liquid biopsy may contribute to the field. We found aberrant lactate dehydrogenase A (LDHA) signaling to be an unfavorable biomarker for PC. Methods: A total of 9 genes of the glycolysis pathway were detected by enrichment analysis in the PC Gene Expression Omnibus (GEO) dataset. The relationship between LDHA/pyruvate kinase (PKM)/ fructose biphosphate aldolase A (ALDOA)/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and patient survival was analyzed by Kaplan-Meier plotting analysis of The Cancer Genome Atlas (TCGA). The detection of changing metabolites in the serum of PC patients was performed using a nuclear magnetic resonance (NMR) spectrometer. Results: We found LDHA was an independent predictor of overall survival (OS) in PC patients (P<0.001). Consistent with genetic aberrance of LDHA, we identified significant alterations in patients' glycolysisrelated metabolites, including upregulation of lactic acid and downregulation of pyruvic acid. A 0.956 area under the curve (AUC) was achieved using the combinative metabolites score of lactic acid, pyruvic acid, citric acid, and glucose to distinguish PC from healthy controls. Conclusions: Aberrant LDHA signaling is an unfavorable biomarker for PC and consequential metabolic changes constitute potential diagnostic signatures of PCs.

Automated summary

The study revealed LDHA as an independent predictor of overall survival in pancreatic cancer patients, with significant alterations in patients' metabolites, including upregulation of lactic acid and downregulation of pyruvic acid. Combining different metabolite scores can effectively distinguish between pancreatic cancer patients and healthy controls.