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Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts

Cited 6 time in Web of Science Cited 7 time in Scopus
Issue Date
2021-08
Citation
Nature Communications, Vol.12 No.1, p. 4840
Abstract
Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies. Gastric cancer is commonly treated by chemotherapy using 5-fluorouracil derivatives and platinum combination, but predictive biomarker remains lacking. Here, the authors develop a 30-gene prediction model to determine the responsiveness to 5-fluorouracil and oxaliplatin-based chemotherapy through the integrative profiling of patient-derived xenografts
ISSN
2041-1723
URI
https://hdl.handle.net/10371/177210
DOI
https://doi.org/10.1038/s41467-021-25122-4
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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