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Updated: May 21, 2025
Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
Published on: June 21, 2018
Bioinformatics Identification of Lactate-Associated Genes in Hepatocellular Carcinoma: G6PD's Role in Immune
Hao-Ran Qu1,2, Chao-Qun Wang3,4, Su-Juan Sun1,2
1State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, China.
Background:
Hepatocellular carcinoma (HCC) is a major global health issue, with poor prognosis often associated with dysregulated metabolic pathways, especially lactate metabolism. This study explored the prognostic significance of lactate-associated genes in HCC and their potential as therapeutic targets.
Methods:
We analyzed RNA-seq and clinical data from 374 patients with HCC from The Cancer Genome Atlas (TCGA) database. Using Cox regression, LASSO analysis, and Kaplan-Meier survival curves, we identified key lactate-associated genes associated with patient outcomes. Functional validations, including Western blot, flow cytometry, and molecular docking studies, were performed to confirm the biological impact of these genes.
Results:
G6PD, IK, and CALML5 were identified as significant prognostic markers for HCC. A prognostic model was developed that effectively stratified patients into risk groups, which correlated with survival. G6PD's role in immune modulation and its potential as a drug target were validated through biochemical assays and computational analyses. Functional assays in HepG2 cells confirmed that alterations in G6PD expression affect T cell activity, with knockdown enhancing IFN-γ production and overexpression inhibiting it, demonstrating G6PD's role in immune evasion.
Conclusions:
This study establishes lactate metabolism genes, particularly G6PD, as key prognostic markers in HCC. The validation of G6PD's immunomodulatory effects further supports its potential as a therapeutic target for strategies aimed at enhancing immune surveillance and treatment outcomes in HCC.
