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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 metabolomic-based liquid biopsy may contribute to the field. We found aberrant lactate dehydrogenase A (LD...

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Autores principales: Jiang, Wenna, Qiao, Lu, Zuo, Duo, Qin, Di, Xiao, Jiawei, An, Haohua, Wang, Yanhui, Zhang, Xinwei, Jin, Yu, Ren, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944301/
https://www.ncbi.nlm.nih.gov/pubmed/33708985
http://dx.doi.org/10.21037/atm-21-295
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author Jiang, Wenna
Qiao, Lu
Zuo, Duo
Qin, Di
Xiao, Jiawei
An, Haohua
Wang, Yanhui
Zhang, Xinwei
Jin, Yu
Ren, Li
author_facet Jiang, Wenna
Qiao, Lu
Zuo, Duo
Qin, Di
Xiao, Jiawei
An, Haohua
Wang, Yanhui
Zhang, Xinwei
Jin, Yu
Ren, Li
author_sort Jiang, Wenna
collection PubMed
description 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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spelling pubmed-79443012021-03-10 Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer Jiang, Wenna Qiao, Lu Zuo, Duo Qin, Di Xiao, Jiawei An, Haohua Wang, Yanhui Zhang, Xinwei Jin, Yu Ren, Li Ann Transl Med Original Article 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. AME Publishing Company 2021-02 /pmc/articles/PMC7944301/ /pubmed/33708985 http://dx.doi.org/10.21037/atm-21-295 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Jiang, Wenna
Qiao, Lu
Zuo, Duo
Qin, Di
Xiao, Jiawei
An, Haohua
Wang, Yanhui
Zhang, Xinwei
Jin, Yu
Ren, Li
Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title_full Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title_fullStr Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title_full_unstemmed Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title_short Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer
title_sort aberrant lactate dehydrogenase a signaling contributes metabolic signatures in pancreatic cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944301/
https://www.ncbi.nlm.nih.gov/pubmed/33708985
http://dx.doi.org/10.21037/atm-21-295
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