Document Type

Article

Publication Date

8-10-2021

Publication Title

Nat Commun

Keywords

Adenocarcinoma, Animals, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Female, Fluorouracil, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Oxaliplatin, Stomach Neoplasms, Survival Analysis, Tumor Burden, Xenograft Model Antitumor Assays

JAX Location

JGM

JAX Source

Nat Commun 2021 Aug 10; 12(1):4840

Volume

12

Issue

1

First Page

4840

Last Page

4840

ISSN

2041-1723

PMID

34376661

DOI

https://doi.org/10.1038/s41467-021-25122-4

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.

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.

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