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Integrated multi-omics reveal lactate metabolism-related gene signatures and PYGL in predicting HNSCC prognosis and immunotherapy efficacy

  • 0Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Bmc Cancer +

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April 24, 2025

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April 24, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed a prognostic model using lactate metabolism genes to predict head and neck cancer survival and immune response. Targeting the gene PYGL may improve immunotherapy efficacy in HNSCC patients.

Area Of Science

  • Oncology
  • Cancer Metabolism
  • Immunology

Background

  • Head and neck squamous cell carcinoma (HNSCC) presents significant treatment challenges.
  • Lactate metabolism is critical in cancer initiation and the tumor microenvironment (TME).
  • The prognostic value of lactate metabolism-related genes (LMRGs) and TME roles in HNSCC need further investigation.

Purpose Of The Study

  • To develop a prognostic multigene signature based on LMRGs for HNSCC.
  • To correlate this signature with immune characteristics and immunotherapy response.
  • To elucidate the role of lactate metabolism and specific genes like PYGL within the HNSCC TME.

Main Methods

  • Construction of a prognostic multigene signature using LMRGs.
  • Correlation analysis with immunological features and immunotherapy efficacy.
  • Single-cell sequencing, immunofluorescence, and in vitro experiments to study PYGL in HNSCC TME.
  • Drug screening for PYGL-targeting agents.

Main Results

  • A robust LMRG-based prognostic signature stratified HNSCC patients by survival (OS, PFS).
  • Low-risk patients showed reduced lactate metabolism, increased CD8+ T cell infiltration, and better immunotherapy response.
  • Tumor cells exhibited the highest lactate metabolism; PYGL was identified as a key prognostic gene, impacting macrophage polarization and CD8+ T cell infiltration.
  • PYGL inhibition reduced lactate and enhanced copper-dependent cell death; elesclomol showed promise against PYGL-knockdown cells.

Conclusions

  • An LMRG-based model accurately predicts HNSCC patient survival and immune microenvironment status.
  • PYGL is a crucial biomarker for prognosis and therapy, regulating lactate metabolism and immune suppression.
  • Targeting PYGL presents a potential strategy to enhance HNSCC immunotherapy efficacy by modulating metabolic and immune landscapes.

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