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

Details

Title
Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts
Author
Deukchae, Na 1 ; Chae Jeesoo 2   VIAFID ORCID Logo  ; Cho Sung-Yup 3 ; Kang Wonyoung 4 ; Lee, Ahra 5 ; Min Seoyeon 5 ; Kang Jinjoo 5 ; Kim Min Jung 6 ; Choi Jaeyong 7 ; Lee, Woochan 7   VIAFID ORCID Logo  ; Shin Dongjin 7 ; Ahrum, Min 8 ; Yu-Jin, Kim 9 ; Kyung-Hun, Lee 10 ; Tae-Yong, Kim 10 ; Suh Yun-Suhk 11 ; Seong-Ho, Kong 12 ; Lee, Hyuk-Joon 13 ; Woo-Ho, Kim 14   VIAFID ORCID Logo  ; Park Hansoo 15   VIAFID ORCID Logo  ; Im Seock-Ah 10 ; Han-Kwang, Yang 13 ; Lee, Charles 16 ; Jong-Il, Kim 3   VIAFID ORCID Logo 

1  Ewha Womans University Mokdong Hospital, Ewha Institute of Convergence Medicine, Seoul, Korea (GRID:grid.411076.5) 
2  Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); The Catholic University of Korea, Cancer Evolution Research Center, Seoul, Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224) 
3  Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Medical Research Center, Genomic Medicine Institute (GMI), Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
4  The Jackson Laboratory for Genomic Medicine, Farmington, USA (GRID:grid.249880.f) (ISNI:0000 0004 0374 0039) 
5  Ewha Womans University, Department of Life Science, Seoul, Korea (GRID:grid.255649.9) (ISNI:0000 0001 2171 7754) 
6  Seoul National University, Medical Research Center, Genomic Medicine Institute (GMI), Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
7  Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
8  Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Hospital, Biomedical Research Institute, Seoul, Republic of Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
9  Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
10  Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
11  Seoul National University College of Medicine, Department of Surgery, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Bundang Hospital, Department of Surgery, Seoul, Korea (GRID:grid.412480.b) (ISNI:0000 0004 0647 3378) 
12  Seoul National University College of Medicine, Department of Surgery, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
13  Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Surgery, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
14  Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Pathology, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
15  Gwangju Institute of Science and Technology (GIST), Department of Biomedical Science and Engineering, Gwangju, Korea (GRID:grid.61221.36) (ISNI:0000 0001 1033 9831) 
16  The Jackson Laboratory for Genomic Medicine, Farmington, USA (GRID:grid.249880.f) (ISNI:0000 0004 0374 0039); Ewha Womans University, Department of Life Science, Seoul, Korea (GRID:grid.255649.9) (ISNI:0000 0001 2171 7754); The First Affiliated Hospital of Xiu’an Jiaotong University, Precision Medicine Center, Shaanxi, People’s Republic of China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-021-25122-4
ProQuest document ID
2559937751
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.