Metabolic heterogeneity affects trastuzumab response and survival in HER2-positive advanced gastric cancer.
Br J Cancer
; 130(6): 1036-1045, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38267634
ABSTRACT
BACKGROUND:
Trastuzumab is the only first-line treatment targeted against the human epidermal growth factor receptor 2 (HER2) approved for patients with HER2-positive advanced gastric cancer. The impact of metabolic heterogeneity on trastuzumab treatment efficacy remains unclear.METHODS:
Spatial metabolomics via high mass resolution imaging mass spectrometry was performed in pretherapeutic biopsies of patients with HER2-positive advanced gastric cancer in a prospective multicentre observational study. The mass spectra, representing the metabolic heterogeneity within tumour areas, were grouped by K-means clustering algorithm. Simpson's diversity index was applied to compare the metabolic heterogeneity level of individual patients.RESULTS:
Clustering analysis revealed metabolic heterogeneity in HER2-positive gastric cancer patients and uncovered nine tumour subpopulations. High metabolic heterogeneity was shown as a factor indicating sensitivity to trastuzumab (p = 0.008) and favourable prognosis at trend level. Two of the nine tumour subpopulations associated with favourable prognosis and trastuzumab sensitivity, and one subpopulation associated with poor prognosis and trastuzumab resistance.CONCLUSIONS:
This work revealed that tumour metabolic heterogeneity associated with prognosis and trastuzumab response based on tissue metabolomics of HER2-positive gastric cancer. Tumour metabolic subpopulations may provide an association with trastuzumab therapy efficacy. CLINICAL TRIAL REGISTRATION The patient cohort was conducted from a multicentre observational study (VARIANZ;NCT02305043).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Br J Cancer
/
Br. j. cancer
/
British journal of cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha
País de publicação:
Reino Unido