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A novel glutamine metabolism-related risk model for prognostic prediction of liver hepatocellular carcinoma

  • 0Operating Theatre, Yixing Branch of Wuxi Medical Center of Nanjing Medical University, Yixing People's Hospital, Yixing, Jiangsu 214200, P.R. China.
Oncology Letters +

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July 4, 2025

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July 4, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Glutamine metabolism significantly impacts liver hepatocellular carcinoma (LIHC) development and progression. A novel prognostic model identifies high-risk LIHC patients with poorer outcomes, highlighting GOT2 as a potential therapeutic target.

Area Of Science

  • Oncology
  • Cancer Metabolism
  • Hepatocellular Carcinoma Research

Background

  • The role of glutamine metabolism in liver hepatocellular carcinoma (LIHC) remains incompletely understood.
  • Investigating glutamine metabolism is crucial for advancing LIHC research and treatment strategies.

Purpose Of The Study

  • To elucidate the role of glutamine metabolism in LIHC development and progression.
  • To identify molecular subtypes of LIHC based on glutamine metabolism.
  • To develop a prognostic model for LIHC patients.

Main Methods

  • Utilized The Cancer Genome Atlas and International Cancer Genome Consortium data for LIHC gene expression and clinical profiles.
  • Applied consensus clustering, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set variation analysis for functional enrichment.
  • Developed a prognostic model using LASSO and Cox regression, validated with proteomic and qPCR data.
  • Assessed glutamate-oxaloacetate transaminase 2 (GOT2) function through in vitro assays.

Main Results

  • Identified two distinct LIHC molecular clusters with unique clinical and immunological features related to glutamine metabolism.
  • Developed a prognostic model dividing patients into high- and low-risk groups, with high-risk associated with higher mutational load and poorer prognosis.
  • Found significantly lower GOT2 protein and mRNA expression in LIHC tissues; GOT2 knockdown enhanced LIHC malignancy.
  • The glutamine metabolism signature accurately predicted LIHC prognosis and immune characteristics.

Conclusions

  • Glutamine metabolism plays a critical role in LIHC tumorigenesis and progression, correlating with poor prognosis.
  • The developed glutamine metabolism-related signature demonstrates accuracy in predicting LIHC patient prognosis and immune status.
  • Downregulated GOT2 expression in LIHC indicates a poor prognosis, suggesting GOT2 as a potential therapeutic target.

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