TY - JOUR
T1 - A 15-layer multi-omics analysis of gastric cancer ecotypes provides therapeutic insights
AU - Clinical Proteomic Tumor Analysis Consortium
AU - Wang, Yuefan
AU - Olsen, Lindsey K.
AU - Jiao, Fenglong
AU - Wang, Chenwei
AU - Jiang, Kevin X.
AU - Dou, Yongchao
AU - Hu, Yingwei
AU - Jiao, Liyuan
AU - Chen, Wenrong
AU - Elizarraras, John M.
AU - Khare, Pratik
AU - Yu, Nengneng
AU - Zhu, Huili
AU - Chen, Lijun
AU - Lih, Tung Shing M.
AU - Eser, Pınar
AU - Martins Rodrigues, Fernanda
AU - Shi, Zhiao
AU - Zhang, Cissy
AU - Yu, Clinton
AU - Heiman, David I.
AU - Liao, Yuxing
AU - Shafer, Paul W.
AU - Choi, Seunghyuk
AU - Choi, Jong Min
AU - Savage, Sara R.
AU - Jaehnig, Eric J.
AU - Lei, Jonathan T.
AU - Sun, Yanling
AU - Peng, Chien Wei
AU - Sun, Zhenyu
AU - Morenkov, Paul
AU - Zhang, Kevin
AU - Geffen, Yifat
AU - Hess, Julian
AU - Kumar-Sinha, Chandan
AU - Mani, D. R.
AU - Ding, Li
AU - Getz, Gad
AU - Li, Qing Kay
AU - Omenn, Gilbert S.
AU - Le, Anne
AU - Hostetter, Galen
AU - Newton, Chelsea J.
AU - Cai, Shuang
AU - Ketchum, Karen A.
AU - Robles, Ana I.
AU - Mesri, Mehdi
AU - Minoo, Parham
AU - Camargo, M. Constanza
AU - An, Eunkyung
AU - Hruban, Ralph H.
AU - Liu, Zaoxing
AU - Thiagarajan, Mathangi
AU - Dohlman, Anders B.
AU - Jin, Ramon U.
AU - Huang, Lan
AU - Chan, Daniel W.
AU - Zhang, Hui
AU - Zhang, Bing
AU - Allapitan, Elleine
AU - Anderson, Matthew
AU - Bathe, Oliver F.
AU - Bolba, Oleksandr
AU - Borresen, Brittney
AU - Borucki, Melissa
AU - Carr, Steven A.
AU - Ciocan, Andra
AU - Crispen, Reese
AU - Davar, Diwakar
AU - Dhanasekaran, Saravana Mohan
AU - Domagalski, Marcin
AU - Edwards, Nathan J.
AU - Fonseca, Rafael
AU - Fulidou, Victoria
AU - Gillette, Michael A.
AU - Goldthwaite, Charles A.
AU - Golubkov, Vladislav
AU - Govindan, Ramaswamy
AU - Kołodziejczak-Guglas, Iga
AU - Le, Toan
AU - Liu, Tao
AU - Lu, Yin
AU - Ma'ayan, Avi
AU - Madan, Rashna
AU - McGarvey, Peter
AU - Murawa, Dawid
AU - Nesvizhskii, Alexey I.
AU - Nyce, Kristen
AU - Nywening, Timothy M.
AU - Pandey, Akhilesh
AU - Parikyan, Kristine
AU - Paulovich, Amanda G.
AU - Piehowski, Paul D.
AU - Pilozzi, Alexander
AU - Potapova, Olga
AU - Revin, Sergiy
AU - Roehrl, Michael
AU - Rohrer, Dan
AU - Semikov, Rostyslav
AU - Shkurupii, Bohdana
AU - Shutack, Yvonne
AU - Thangudu, Ratna R.
AU - Tsankov, Tsanko
AU - Tyner, Jeffrey W.
AU - Vatanian, Negin
AU - Vucic, Miodrag
AU - Wang, Pei
AU - Williams, Bart O.
AU - Wiznerowicz, Maciej
AU - Zhang, Tongwu
AU - Zhang, Xu
N1 - Publisher Copyright:
© 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026/5/19
Y1 - 2026/5/19
N2 - Gastric cancer is marked by profound molecular and microenvironmental heterogeneity that limits therapeutic progress. Here, we present a 15-layer multi-omics atlas that integrates genomics, epigenomics, transcriptomics, proteomics, multiple post-translational modifications (PTMs), protein-protein interactions, metabolomics, and microbiome profiles from 159 primary gastric adenocarcinomas and 30 matched normal adjacent tissues. Using cell-state deconvolution, we define tumor ecotypes that refine genomic and histological subtypes by capturing distinct tumor microenvironment architectures linked to clinical outcomes and potential associations with immunotherapy response. Multi-omics integration prioritizes genomic and epigenomic aberrations and their associated vulnerabilities; defines ecotype-specific transcriptional programs, signaling pathways, PTMs, protein interaction networks, and metabolic regulation; and identifies microbiome features linked to ecotypes and resistance pathways. We further prioritize ecotype-, genomic subtype-, and cell type-specific targetable proteins using proteomic and PTM analyses within a tumor microenvironment context. This comprehensive atlas provides a systems-level blueprint for decoding gastric cancer heterogeneity and advancing precision oncology.
AB - Gastric cancer is marked by profound molecular and microenvironmental heterogeneity that limits therapeutic progress. Here, we present a 15-layer multi-omics atlas that integrates genomics, epigenomics, transcriptomics, proteomics, multiple post-translational modifications (PTMs), protein-protein interactions, metabolomics, and microbiome profiles from 159 primary gastric adenocarcinomas and 30 matched normal adjacent tissues. Using cell-state deconvolution, we define tumor ecotypes that refine genomic and histological subtypes by capturing distinct tumor microenvironment architectures linked to clinical outcomes and potential associations with immunotherapy response. Multi-omics integration prioritizes genomic and epigenomic aberrations and their associated vulnerabilities; defines ecotype-specific transcriptional programs, signaling pathways, PTMs, protein interaction networks, and metabolic regulation; and identifies microbiome features linked to ecotypes and resistance pathways. We further prioritize ecotype-, genomic subtype-, and cell type-specific targetable proteins using proteomic and PTM analyses within a tumor microenvironment context. This comprehensive atlas provides a systems-level blueprint for decoding gastric cancer heterogeneity and advancing precision oncology.
KW - gastric cancer
KW - metabolomics
KW - microbiome
KW - multi-omics
KW - post-translational modifications
KW - precision oncology
KW - protein-protein interactions
KW - proteogenomics
KW - therapeutic targets
KW - tumor ecotypes
KW - tumor microenvironment
UR - https://www.scopus.com/pages/publications/105038934985
U2 - 10.1016/j.xcrm.2026.102756
DO - 10.1016/j.xcrm.2026.102756
M3 - Article
C2 - 42013851
AN - SCOPUS:105038934985
SN - 2666-3791
VL - 7
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 5
M1 - 102756
ER -