Related Experiment Video

Updated: Jul 3, 2026

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
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Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence

Published on: October 25, 2011

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Metabolic heterogeneity affects trastuzumab response and survival in HER2-positive advanced gastric cancer

Jun Wang1, Na Sun1, Thomas Kunzke1

  • 1Research Unit Analytical Pathology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

British Journal of Cancer
|January 24, 2024
PubMed
Abstract

Insights

Metabolic heterogeneity in HER2-positive gastric cancer predicts response to trastuzumab. Higher heterogeneity correlates with better prognosis and sensitivity to this targeted therapy, offering new insights for treatment strategies.

Area of Science:

  • Oncology
  • Metabolomics
  • Cancer Research

Background:

  • Trastuzumab is the sole first-line therapy targeting human epidermal growth factor receptor 2 (HER2) for HER2-positive advanced gastric cancer.
  • The influence of metabolic heterogeneity on trastuzumab efficacy is not well understood.

Purpose of the Study:

  • To investigate the association between metabolic heterogeneity and trastuzumab treatment response in HER2-positive advanced gastric cancer.
  • To identify potential metabolic subpopulations linked to treatment outcomes.

Main Methods:

  • Spatial metabolomics using high mass resolution imaging mass spectrometry on pretherapeutic biopsies.
  • K-means clustering to analyze metabolic heterogeneity and identify tumor subpopulations.
  • Simpson's diversity index to quantify metabolic heterogeneity levels.

Main Results:

  • Metabolic heterogeneity was identified in HER2-positive gastric cancer patients, revealing nine distinct tumor subpopulations.
  • High metabolic heterogeneity correlated significantly with trastuzumab sensitivity (p=0.008) and showed a trend towards favorable prognosis.
  • Specific subpopulations were linked to either favorable prognosis/trastuzumab sensitivity or poor prognosis/resistance.

Conclusions:

  • Tumor metabolic heterogeneity, assessed by tissue metabolomics, is associated with prognosis and trastuzumab response in HER2-positive gastric cancer.
  • Distinct tumor metabolic subpopulations may serve as predictive biomarkers for trastuzumab therapy efficacy.

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