TY - JOUR
T1 - Metabolic heterogeneity affects trastuzumab response and survival in HER2-positive advanced gastric cancer
AU - Wang, Jun
AU - Sun, Na
AU - Kunzke, Thomas
AU - Shen, Jian
AU - Feuchtinger, Annette
AU - Wang, Qian
AU - Meixner, Raphael
AU - Gleut, Ronan Le
AU - Haffner, Ivonne
AU - Luber, Birgit
AU - Lordick, Florian
AU - Walch, Axel
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/4/6
Y1 - 2024/4/6
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85182997626&partnerID=8YFLogxK
U2 - 10.1038/s41416-023-02559-6
DO - 10.1038/s41416-023-02559-6
M3 - Article
AN - SCOPUS:85182997626
SN - 0007-0920
VL - 130
SP - 1036
EP - 1045
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 6
ER -
