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Exosomal PKM2: A Noninvasive Diagnostic Marker Linking Macrophage Metabolic Reprogramming to Gastric Cancer Pathogenesis

  • 0Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Cancer Science +

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March 24, 2025

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March 24, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Plasma exosomal pyruvate kinase isoenzyme type M2 (PKM2) shows promise as a biomarker for early gastric cancer (GC) diagnosis and predicting poor prognosis. It also promotes GC progression by activating lipid synthesis in tumor-associated macrophages.

Area Of Science

  • Oncology
  • Biomarkers
  • Cancer Biology

Background

  • Tumor-derived exosomes (TDEs) are crucial cancer biomarkers.
  • The role of exosomal pyruvate kinase isoenzyme type M2 (PKM2) in gastric cancer (GC) diagnosis, prognosis, and mechanism is unclear.

Purpose Of The Study

  • To investigate plasma exosomal PKM2 as a diagnostic and prognostic biomarker for GC.
  • To elucidate the mechanism by which exosomal PKM2 promotes GC development.

Main Methods

  • Analysis of plasma exosomal PKM2 in 216 samples from GC patients and healthy donors.
  • Kaplan-Meier analysis for prognosis.
  • Single-cell transcriptome sequencing to identify PKM2-enriched cells.
  • In vitro experiments to confirm TAM polarization and GC cell behavior.

Main Results

  • Plasma exosomal PKM2 showed superior diagnostic performance for early GC compared to existing biomarkers.
  • High exosomal PKM2 expression correlated with poor GC prognosis.
  • Exosomal PKM2 induced M2 polarization of tumor-associated macrophages (TAM), promoting GC cell proliferation, migration, and invasion.
  • Exosomal PKM2 enhanced lipid synthesis in TAM via the SCAP/SREBP1 pathway.

Conclusions

  • Plasma exosomal PKM2 is a potential novel biomarker for GC clinical diagnosis.
  • Exosomal PKM2 contributes to GC development by modulating the tumor microenvironment through the SREBP1-related lipid synthesis pathway in macrophages.

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