Aberrant Lactate Dehydrogenase A Signaling Contributes Metabolic Signatures in Pancreatic Cancer

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2021 Mar 12

PMID 33708985

Citations 5

Authors

Wenna Jiang

Lu Qiao

Duo Zuo

Di Qin

Jiawei Xiao

Haohua An

Yanhui Wang

Xinwei Zhang

Yu Jin

Li Ren

Affiliations

Soon will be listed here.

Abstract

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 metabolomic-based 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' glycolysis-related 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.

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