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PAF signaling axis functions as biomarker or target for esophageal squamous cell carcinoma diagnosis or treatment

  • 0State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China; Peking University International Cancer Institute, Peking University, Beijing 100191, China.
Cancer Letters +

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July 20, 2025

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July 20, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Platelet-activating factor (PAF) in plasma can indicate lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Ginkgetin, a natural compound, shows potential for treating ESCC by inhibiting PAF signaling pathways.

Area Of Science

  • Oncology
  • Metabolism
  • Immunology

Background

  • Dysregulated lipid metabolism is a hallmark of cancer, promoting tumorigenesis and malignancy.
  • Platelet-activating factor (PAF) is a lipid mediator that stimulates inflammation and aggressive progression in esophageal squamous cell carcinoma (ESCC).

Purpose Of The Study

  • To investigate the role of PAF and its downstream signaling in ESCC metastasis and malignancy.
  • To evaluate PAF as a potential biomarker for lymph node (LN) metastasis in ESCC.
  • To explore ginkgetin as a therapeutic agent targeting the PAF axis in ESCC.

Main Methods

  • Plasma PAF levels were measured and correlated with LN metastasis status.
  • Olink assay was used to identify plasma cytokines associated with LN metastasis.
  • RNA-sequencing and immunohistochemistry (IHC) were performed on ESCC cell lines and clinical samples.
  • In vitro and in vivo studies evaluated the therapeutic effects of ginkgetin on ESCC models.

Main Results

  • Plasma PAF levels correlated with LN metastasis in ESCC patients.
  • Elevated levels of cytokines like IL-8, CXCL1, CXCL5, and CXCL11 were associated with LN metastasis and correlated with PAF levels.
  • PAF signaling promoted the expression of inflammatory cytokines and tumor-promoting molecules in ESCC.
  • Ginkgetin inhibited PAF-mediated JAK2/STAT3 activation, downstream cytokine expression, glycolysis, and tumor cell malignancy with minimal toxicity.

Conclusions

  • PAF serves as a potential biomarker for evaluating LN metastasis in ESCC.
  • Ginkgetin demonstrates significant antitumor effects against ESCC by suppressing PAF-driven signaling pathways, suggesting its therapeutic potential.

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