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

Title
Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts
Authors
Lee A.Min S.Kang J.Kim M.J.Choi J.Lee W.Shin D.Min A.Kim Y.-J.Lee K.-H.Kim T.-Y.Suh Y.-S.Kong S.-H.Lee H.-J.Kim W.-H.Park H.Im S.-A.Yang H.-K.Lee C.Kim J.-I.Na D.Chae J.Cho S.-Y.Kang W.
Ewha Authors
Charles Lee나득채
SCOPUS Author ID
Charles Leescopus
Issue Date
2021
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
Nature Communications vol. 12, no. 1
Publisher
Nature Research
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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. © 2021, The Author(s).
DOI
10.1038/s41467-021-25122-4
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자연과학대학 > 생명과학전공 > Journal papers
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