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Blood Biomarker-Based Predictive Indicator for Liver Metastasis in Alpha-Fetoprotein-Producing Gastric Cancer and

Yongfeng Ding1, Yiran Chen2, Jing Zhang2

  • 1Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 28, 2025
PubMed
Summary

A new blood biomarker, the ANLiM score, predicts liver metastasis and immunotherapy response in alpha-fetoprotein-producing gastric cancer (AFPGC). This score aids in understanding the immunosuppressive tumor microenvironment and optimizing treatment strategies.

Keywords:
alpha‐fetoprotein‐producing gastric cancerimmunotherapyliver metastasistumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Biomarker Development

Background:

  • Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare, aggressive subtype with high liver metastasis risk.
  • The tumor microenvironment (TME) in AFPGC is complex and poorly understood, impacting treatment outcomes.

Purpose of the Study:

  • To develop a predictive indicator for liver metastasis in AFPGC.
  • To investigate the TME characteristics of AFPGC with liver metastasis.
  • To explore the potential of biomarkers for predicting immunotherapy response.

Main Methods:

  • Multicenter retrospective study of 317 AFPGC patients.
  • Development of the ANLiM score using alpha-fetoprotein (AFP) and neutrophil-lymphocyte ratio (NLR).
  • Integrated multi-omics analysis (whole-exome sequencing, proteomics, single-cell RNA sequencing) and multiplex immunofluorescence.
  • Validation in a cohort receiving anti-programmed cell death 1 (anti-PD-1) therapy.

Main Results:

  • The ANLiM score effectively predicts liver metastasis in AFPGC.
  • AFPGC with liver metastasis exhibits an immunosuppressive TME, involving tumor-associated neutrophils and tertiary lymphoid structures.
  • The ANLiM score also predicts response to anti-PD-1 immunotherapy.
  • Validation confirmed the ANLiM score's predictive value for immunotherapy efficacy.

Conclusions:

  • The ANLiM score is a novel, easily applicable biomarker for predicting liver metastasis and immunotherapy response in AFPGC.
  • Understanding the immunosuppressive TME in AFPGC provides insights for refining immunotherapy strategies.
  • This blood biomarker-based indicator offers a promising tool for personalized treatment in AFPGC.