Metabolic heterogeneity affects trastuzumab response and survival in HER2-positive advanced gastric cancer
Menée à partir d'échantillons biopsiques prélevés avant traitement sur des patients atteints d'un cancer de l'estomac HER2+ de stade avancé et menée à l'aide de l'imagerie à haute résolution par spectrométrie de masse, cette étude met en évidence une hétérogénéité métabolique qui affecte la réponse tumorale au trastuzumab et la survie des patients
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).
British Journal of Cancer , article en libre accès, 2024